A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
- Conditions
- Neoplasms
- Interventions
- Registration Number
- NCT04607421
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab) taken alone or together with standard chemotherapy for the potential treatment of colorectal cancer that:
* has spread to other parts of the body (metastatic);
* has a certain type of abnormal gene called "BRAF"; and
* has not received prior treatment.
Participants in this study will receive one of the following study treatments:
* Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection into the vein) at the study clinic.
* Encorafenib plus cetuximab with chemotherapy: These participants will receive encorafenib and cetuximab in the way described in the bullet above. Additionally, they will receive standard chemotherapy by IV infusion and oral treatment at home.
* Chemotherapy alone: These participants will receive chemotherapy, the standard treatment for this condition, by IV infusion at the study clinics and oral treatment at home.
This study is currently enrolling participants who will receive either encorafenib plus cetuximab with chemotherapy or chemotherapy alone.
The study team will monitor how each participant responds to the study treatment for up to about 3 years.
- Detailed Description
The purpose of the study is to evaluate whether encorafenib plus cetuximab (EC), alone or in combination with chemotherapy, can improve clinical outcomes relative to current standard of-care chemotherapy in participants with previously untreated BRAF V600E-mutant mCRC. Since encorafenib has not previously been combined with chemotherapy, the tolerability and PK of EC in combination with mFOLFOX6 and in combination with FOLFIRI will be evaluated in separate cohorts in the safety lead-in portion of the trial in order to identify which chemotherapy combination is to be used in the Phase 3 portion of the study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 827
- Safety Lead-In = Male/female ≥ 18 years old
- Phase 3 and Cohort 3: Male/female ≥ 16 years old (where permitted locally)
- Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E mutation
- Prior systemic treatment in metastatic setting: 0-1 regimens for Safety Lead In; none for Phase 3 and Cohort 3. (Note: Prior adjuvant or neoadjuvant therapy considered metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant treatment )
- Measurable disease (Phase 3 and Cohort 3)/ Measurable or evaluable disease (Safety Lead-in)
- ECOG PS 0-1
- Adequate organ function
- Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is ineligible to receive immune checkpoint inhibitors due to a pre-existing medical condition
- Active bacterial or viral infections in 2 weeks prior to starting dosing
- Symptomatic brain metastases
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Safety Lead-in Cohort 1 Encorafenib Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 1 Cetuximab Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 1 Irinotecan Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 1 Leucovorin Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 1 5-FU Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 2 Encorafenib Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 2 Cetuximab Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 2 Oxaliplatin Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 2 Leucovorin Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Safety Lead-in Cohort 2 5-FU Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Phase 3 Arm A Encorafenib Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Phase 3 Arm A Cetuximab Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Phase 3 Arm B Encorafenib Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Phase 3 Arm B Cetuximab Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Phase 3 Arm B Oxaliplatin Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Phase 3 Arm B Leucovorin Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Phase 3 Arm B 5-FU Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Phase 3 Arm C Oxaliplatin Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions) Phase 3 Arm C Irinotecan Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions) Phase 3 Arm C Leucovorin Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions) Phase 3 Arm C 5-FU Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions) Phase 3 Arm C Capecitabine Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions) Phase 3 Arm C Bevacizumab Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions) Cohort 3 Arm D Encorafenib Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Cohort 3 Arm D Cetuximab Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Cohort 3 Arm D Irinotecan Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Cohort 3 Arm D Leucovorin Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Cohort 3 Arm D 5-FU Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks Cohort 3 Arm E Irinotecan Irinotecan 180 mg/m2 (90-minute IV infusion) every 2 weeks, Leucovorin 400 mg/m2 (120-minute IV infusion) every 2 weeks, 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks, Bevacizumab (optional; given per prescribing instructions) Cohort 3 Arm E Leucovorin Irinotecan 180 mg/m2 (90-minute IV infusion) every 2 weeks, Leucovorin 400 mg/m2 (120-minute IV infusion) every 2 weeks, 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks, Bevacizumab (optional; given per prescribing instructions) Cohort 3 Arm E 5-FU Irinotecan 180 mg/m2 (90-minute IV infusion) every 2 weeks, Leucovorin 400 mg/m2 (120-minute IV infusion) every 2 weeks, 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks, Bevacizumab (optional; given per prescribing instructions) Cohort 3 Arm E Bevacizumab Irinotecan 180 mg/m2 (90-minute IV infusion) every 2 weeks, Leucovorin 400 mg/m2 (120-minute IV infusion) every 2 weeks, 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks, Bevacizumab (optional; given per prescribing instructions)
- Primary Outcome Measures
Name Time Method Safety Lead-in Study: Incidence of Dose Limiting Toxicities (DLTs) After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months Incidence of dose limiting toxicity defined as any adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment
Phase 3: Progression free survival, by blinded independent review Duration of Phase 3, approximately 36 months Progression free survival, defined as the time from the date of randomization to the earliest documented disease progression or death due to any cause: encorafenib and cetuximab + mFOLFOX6 (Arm B) vs the Control Arm (Arm C)
Phase 3: Objective response rate by blinded independent review Duration of Phase 3, approximately 23 months Objective response defined as complete response (CR), or partial response (PR) according to RECIST v1.1 based on BICR assessment, from the date of randomization until the date of the first documentation of progression of disease (PD)
Cohort 3: Objective response rate by blinded independent review Duration of Cohort 3, approximately 15 months. Defined as CR, or PR according to RECIST v1.1 based on BICR assessment, from the date of randomization until the date of the first documentation of PD, death or start of new anticancer therapy
- Secondary Outcome Measures
Name Time Method Safety Lead-in: Incidence of adverse events After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months An adverse event is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship as assessed by CTCAE 4.03
Safety Lead-in: Incidence of abnormal clinical laboratory parameters, abnormal vital signs and abnormal electrocardiograms After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months Changes in clinical laboratory parameters, vital signs and electrocardiograms determined clinically significant at the investigator's discretion.
Safety Lead-in: Incidence of dose interruptions, dose modifications and discontinuations due to adverse events After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months Safety Lead-in: Overall response rate by investigator After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months Overall response rate, defined as the proportion of participants who have achieved a confirmed best overall response per RECIST v1.1: encorafenib and cetuximab + mFOLFOX6 or FOLFIRI
Safety Lead-in: Duration of response by Investigator After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months Duration of response, defined as the time from the date of first radiographic evidence of response to the earliest documented disease progression per RECIST v1.1, or death due to any cause: encorafenib and cetuximab + mFOLFOX6 or FOLFIRI
Safety Lead-in:Progression free survival by Investigator After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months Progression free survival, defined as the time from the first dose to the earliest documented disease progression per RECIST v1.1, or death due to any cause: encorafenib and cetuximab + mFOLFOX6 or FOLFIRI
Safety Lead-in: Time to response by Investigator After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 12 months Time to response, defined as the time from first dose to first radiographic evidence of response per RECIST v1.1: encorafenib and cetuximab + mFOLFOX6 or FOLFIRI
Safety Lead-in: Overall survival After 30 evaluable patients in each cohort complete 1 cycle (up to 28 days), approximately 36 months Overall survival defined as the time from the first dose to death due to any cause: encorafenib and cetuximab + mFOLFOX6 or FOLFIRI
Phase 3: Overall survival Duration of Phase 3, approximately 50 months Overall survival, defined as the time from the date of randomization to death due to any cause: encorafenib + cetuximab (Arm A) vs Control Arm (Arm C) and encorafenib + cetuximab +mFOLFOX6 (Arm B) vs Control Arm (Arm C) and encorafenib + cetuximab (Arm A) vs encorafenib + cetuximab +mFOLFOX6 (Arm B)
Phase 3: Overall response rate by Investigator and by blinded independent review Duration of Phase 3, approximately 36 months Overall response rate, defined as the proportion of participants who have achieved a confirmed best overall response per RECIST v1.1: encorafenib + cetuximab (Arm A) vs Control Arm (Arm C) and encorafenib + cetuximab +mFOLFOX6 (Arm B) vs Control Arm (Arm C) and encorafenib + cetuximab (Arm A) vs encorafenib + cetuximab +mFOLFOX6 (Arm B)
Phase 3: Duration of response by Investigator and blinded independent review Duration of Phase 3, approximately 36 months Duration of response, defined as the time from the date of first radiographic evidence of response to the earliest documented disease progression per RECIST v1.1, or death due to any cause: encorafenib + cetuximab (Arm A) vs Control Arm (Arm C) and encorafenib + cetuximab +mFOLFOX6 (Arm B) vs Control Arm (Arm C) and encorafenib + cetuximab (Arm A) vs encorafenib + cetuximab +mFOLFOX6 (Arm B)
Phase 3: Time to response by blinded independent review and by Investigator Duration of Phase 3, approximately 36 months Time to response, defined as the time from first dose to first radiographic evidence of response per RECIST v1.1: encorafenib + cetuximab (Arm A) vs Control Arm (Arm C) and encorafenib + cetuximab +mFOLFOX6 (Arm B) vs Control Arm (Arm C) and encorafenib + cetuximab (Arm A) vs encorafenib + cetuximab +mFOLFOX6 (Arm B)
Phase 3: Progression free survival by Investigator and by blinded independent review Duration of Phase 3, approximately 36 months Progression free survival, defined as the time from the first dose to the earliest documented disease progression per RECIST v1.1, or death due to any cause:: encorafenib + cetuximab (Arm A) vs Control Arm (Arm C) and encorafenib + cetuximab +mFOLFOX6 (Arm B) vs Control Arm (Arm C) and encorafenib + cetuximab (Arm A) vs encorafenib + cetuximab +mFOLFOX6 (Arm B)
Phase 3: Progression free survival 2 by Investigator Duration of Phase 3, approximately 36 months Progression free survival 2, defined as the time from the date of randomization to the second objective disease progression per RECIST v1.1, or death from any cause, whichever occurs first: encorafenib + cetuximab (Arm A) vs Control Arm (Arm C) and encorafenib + cetuximab +mFOLFOX6 (Arm B) vs Control Arm (Arm C) and encorafenib + cetuximab (Arm A) vs encorafenib + cetuximab +mFOLFOX6
Phase 3: Incidence of adverse events Duration of Phase 3, approximately 36 months An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship: encorafenib + cetuximab (Arm A) and encorafenib + cetuximab +mFOLFOX6 (Arm B)
Phase 3: Incidence of abnormal clinical laboratory parameters, abnormal vital signs and abnormal electrocardiograms Duration of Phase 3, approximately 36 months Changes in clinical laboratory parameters, vital signs and electrocardiograms determined clinically significant at the investigator's discretion: encorafenib + cetuximab (Arm A) and encorafenib + cetuximab +mFOLFOX6 (Arm B)
Phase 3: Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) Duration of Phase 3, approximately 36 months EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Phase 3: Change from Baseline in the EuroQol-5D-5L (EQ-5D-5L) Questionnaire Duration of Phase 3, approximately 36 months The EQ-5D-5L is a standardized measure of health utility that provides a single index value for the participant's health status. It is frequently used for economic evaluations of health care and has been shown to be a valid and reliable instrument, and comprises a short descriptive system questionnaire and a visual analogue scale (EQ VAS) that are cognitively undemanding, taking about 2 minutes to complete
Phase 3: Change from Baseline in the Patient Global Impression of Severity (PGIS) Duration of Phase 3, approximately 36 months The PGIS is a single-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time.
Phase 3: Change from Baseline in the Patient Global Impression of Change (PGIC) questionnaires Duration of Phase 3, approximately 36 months The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change in symptoms or quality of life since starting treatment.
Phase 3: Confirm the MSI-status in tumor tissue Once, pre-treatment Summarize MSI-status as determined by retrospective central testing of baseline tumor tissue
Phase 3: To determine the correlation between ctDNA levels, BRAF V600 alterations, and clinical outcome Predose on Cycle 1 Day 1, 15, Cycle 2 Day 15, Cycle 7 Day 1 and EOT. Arm C sampling on Day 1 of Cycles 1-3, 9 and EOT. EOT is approx 36 months. ctDNA levels and BRAF V600 VAF from ctDNA analysis of plasma samples collected at baseline and on treatment
Safety Lead-in: Maximum plasma concentration of encorafenib, LHY746, irinotecan and SN-38 Cycle 1 Day 1 and Day 15: predose, and 0.75, 1.5, 2.5, 3.5, 5.5 and 7.5 hours after dosing, Cycle 1 Day 3 and Day 17:predose and Cycle 2 through Cycle 6: Day 1 predose. Each cycle is 28 days Safety Lead-in: Area under the plasma concentration time curve of encorafenib, LHY746, irinotecan and SN-38 Cycle 1 Day 1 and Day 15: predose, and 0.75, 1.5, 2.5, 3.5, 5.5 and 7.5 hours after dosing, Cycle 1 Day 3 and Day 17:predose and Cycle 2 through Cycle 6: Day 1 predose. Each cycle is 28 days. Safety Lead-in: Time to maximim plasma concentration time curve of encorafenib, LHY746, irinotecan and SN-38 Cycle 1 Day 1 and Day 15: predose, and 0.75, 1.5, 2.5, 3.5, 5.5 and 7.5 hours after dosing, Cycle 1 Day 3 and Day 17:predose and Cycle 2 through Cycle 6: Day 1 predose. Each cycle is 28 days Safety Lead-in: Maximum plasma concentration of encorafenib, LHY746 and oxaliplatin Cycle 1 Day 1 and Day 15: predose, and 1, 2, 3, 4, 6 and 8 hours after dosing, Cycle 1 Day 3 and Day 17: predose and Cycle 2 through Cycle 6: Day 1 predose. Each cycle is 28 days Safety Lead-in: Area under the plasma concentration time curve of encorafenib, LHY746 and oxaliplatin Cycle 1 Day 1 and Day 15: predose, and 1, 2, 3, 4, 6 and 8 hours after dosing, Cycle 1 Day 3 and Day 17: predose and Cycle 2 through Cycle 6: Day 1 predose. Each cycle is 28 days Safety Lead-in: Clearance of irinotecan, SN-38 and oxaliplatin Cycle 1 Day 1 and Day 15: predose, and 0.75, 1.5, 2.5, 3.5, 5.5 and 7.5 hours after dosing, Cycle 1 Day 3 and Day 17:predose and Cycle 2 through Cycle 6: Day 1 predose. Each cycle is 28 days Changes in exposures of irinotecan and its metabolite (SN-38) on Cycle 1 Day 15 compared to Cycle 1 Day 1 in Cohort 1 (encorafenib and cetuximab + FOLFIRI) Changes in exposures of oxaliplatin on Cycle 1 Day 15 compared to Cycle 1 Day 1 in Cohort 2 (encorafenib and cetuximab + mFOLFOX6)
Safety Lead-in: Time to maximim plasma concentration time curve of encorafenib, LHY746 and oxaliplatin Cycle 1 Day 1 and Day 15: predose, and 1, 2, 3, 4, 6 and 8 hours after dosing, Cycle 1 Day 3 and Day 17: predose and Cycle 2 through Cycle 6: Day 1 predose. Each cycle is 28 days Phase 3: Trough concentrations of encorafenib and its metabolite LHY746 Predose on Cycle 1 through Cycle 6. Each cycle is 28 days Trough plasma concentrations in all patients in Arm A and Arm B
Cohort 3: Progression free survival by Investigator and by blinded independent review Duration of Cohort 3, approximately 21 months Progression free survival, defined as the time from the first dose to the earliest documented disease progression per RECIST v1.1, or death due to any cause.
Cohort 3: Overall response rate by investigator Duration of Cohort 3, approximately 21 months Overall response rate, defined as the proportion of participants who have achieved a confirmed best overall response per RECIST v 1.1
Cohort 3: Duration of response by Investigator and by blinded independent review Duration of Cohort 3, approximately 21 months Duration of response, defined as the time from the date of first radiographic evidence of response to the earliest documented disease progression per RECIST v1.1, or death due to any cause
Cohort 3: Time to response by Investigator and by blinded independent review Duration of Cohort 3, approximately 21 months Time to response, defined as the time from the date of randomization to first radiographic evidence of response per RECIST v1.1
Cohort 3: Overall survival Duration of Cohort 3, approximately 36 months Overall survival, defined as the time from the date of randomization to death due to any cause
Cohort 3: Incidence of adverse events Duration of Cohort 3, approximately 21 months An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship: encorafenib + cetuximab (Arm A) and encorafenib + cetuximab +mFOLFOX6 (Arm B)
Cohort 3: Incidence of abnormal clinical laboratory parameters, abnormal vital signs and abnormal electrocardiograms Duration of Cohort 3, approximately 21 months Changes in clinical laboratory parameters, vital signs and electrocardiograms determined clinically significant at the investigator's discretion: encorafenib + cetuximab (Arm A) and encorafenib + cetuximab +mFOLFOX6 (Arm B)
Cohort 3: Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) Duration of Cohort 3, approximately 21 months EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Cohort 3: Change from Baseline in the EuroQol-5D-5L (EQ-5D-5L) Questionnaire Duration of Cohort 3, approximately 21 months The EQ-5D-5L is a standardized measure of health utility that provides a single index value for the participant's health status. It is frequently used for economic evaluations of health care and has been shown to be a valid and reliable instrument, and comprises a short descriptive system questionnaire and a visual analogue scale (EQ VAS) that are cognitively undemanding, taking about 2 minutes to complete
Cohort 3: Change from Baseline in the Patient Global Impression of Severity (PGIS) Duration of Cohort 3, approximately 21 months The PGIS is a single-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time.
Cohort 3: Change from Baseline in the Patient Global Impression of Change (PGIC) questionnaires Duration of Cohort 3, approximately 21 months The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change in symptoms or quality of life since starting treatment.
Cohort 3: Confirm the MSI-status in tumor tissue Once, pre-treatment Summarize MSI-status as determined by retrospective central testing of baseline tumor tissue
Cohort 3: To determine the correlation between ctDNA levels, BRAF V600 alterations, and clinical outcome Predose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 15, Cycle 7 Day 1 and End of Treatment (Duration of Cohort 3, approximately 21 months). Each cycle is 28 days. ctDNA levels and BRAF V600 VAF from ctDNA analysis of plasma samples collected at baseline and on treatment
Cohort 3: Trough concentrations of encorafenib and its metabolite LHY746 Predose on Cycle 1 through Cycle 6. Each cycle is 28 days Trough plasma concentrations in all patients in Arm D
Trial Locations
- Locations (267)
Siteman Cancer Center - North County
🇺🇸Florissant, Missouri, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Mayo Clinic in Arizona - Scottsdale
🇺🇸Scottsdale, Arizona, United States
Keck Hospital of USC
🇺🇸Los Angeles, California, United States
LAC & USC Medical Center
🇺🇸Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Keck Hospital of USC Pasadena
🇺🇸Pasadena, California, United States
Mount Sinai Comprehensive Cancer Center, Aventura
🇺🇸Aventura, Florida, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
BRCR Global
🇺🇸Plantation, Florida, United States
BRCR Medical Center Inc.
🇺🇸Plantation, Florida, United States
UChicago Medicine - River East
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
UChicago Medicine at Ingalls - Flossmoor
🇺🇸Flossmoor, Illinois, United States
UChicago Medicine Ingalls Memorial
🇺🇸Harvey, Illinois, United States
University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
🇺🇸New Lenox, Illinois, United States
The University of Chicago Medicine Center for Advanced Care Orland Park
🇺🇸Orland Park, Illinois, United States
UChicago Medicine at Ingalls - Tinley Park
🇺🇸Tinley Park, Illinois, United States
Ochsner Clinic Foundation Research Pharmacy
🇺🇸New Orleans, Louisiana, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Barnes- Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - St Peters
🇺🇸Saint Peters, Missouri, United States
Oncology Hematology West PC dba Nebraska Cancer Specialists
🇺🇸Papillion, Nebraska, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists - IP Storage
🇺🇸Omaha, Nebraska, United States
Memorial Sloan Kettering Cancer Center - Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Summit Medical Group
🇺🇸Florham Park, New Jersey, United States
Memorial Sloan Kettering Cancer Center- Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center- Bergen
🇺🇸Montvale, New Jersey, United States
Memorial Sloan Kettering Cancer Center Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center - Westchester
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center - Main Campus
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center- Nassau
🇺🇸Uniondale, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Martha Morehouse Medical Plaza
🇺🇸Columbus, Ohio, United States
The James Outpatient Care West Campus
🇺🇸Columbus, Ohio, United States
University of Oklahoma Health Sciences Center, OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
🇺🇸Cleveland, Ohio, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
The Ohio State University James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Stefanie Spielman Comprehensive Breast Cancer
🇺🇸Columbus, Ohio, United States
Providence Cancer Institute Franz Clinic
🇺🇸Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
The West Clinic. PLLC. dba West Cancer Center
🇺🇸Germantown, Tennessee, United States
Henry-Joyce Cancer Center
🇺🇸Nashville, Tennessee, United States
Providence Onc and Heme Care Clinic - Westside
🇺🇸Portland, Oregon, United States
Providence St Vincent Medical Center
🇺🇸Portland, Oregon, United States
UPMC Hillman Cancer Center Investigational Drug Service
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Vanderbilt Oncology IDS Pharmacy
🇺🇸Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
VCU Health - Adult Outpatient Pavilion (AOP) Investigational Drug Services
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Wisconsin Clinical Science Center
🇺🇸Madison, Wisconsin, United States
Centro Medico San Roque
🇦🇷San Miguel De Tucumán, Tucumán, Argentina
Instituto Médico Especializado Alexander Fleming
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Clinica Universitaria Reina Fabiola
🇦🇷Cordoba, Argentina
Hospital Privado Centro Médico de Córdoba
🇦🇷Cordoba, Argentina
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
GenesisCare - North Shore
🇦🇺St Leonards, New South Wales, Australia
GenesisCare North Shore
🇦🇺St Leonards, New South Wales, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
The Queen Elizabeth Hospital
🇦🇺Adelaide, South Australia, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
Université Libre de Bruxelles - Hôpital Erasme
🇧🇪Brussels, Bruxelles-capitale, Région DE, Belgium
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Bruxelles-capitale, Région DE, Belgium
Grand Hôpital de Charleroi
🇧🇪Charleroi, Hainaut, Belgium
AZ Groeninge Campus Kennedylaan
🇧🇪Kortrijk, West-vlaanderen, Belgium
ZNA Middelheim
🇧🇪Antwerpen, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
🇧🇪Liège, Belgium
GZA Hospitals Campus Sint Augustinus
🇧🇪Wilrijk, Belgium
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
🇧🇷Rio de Janeiro, RJ, Brazil
Reichow - Centro de Ensino e Pesquisa
🇧🇷Blumenau, Santa Catarina, Brazil
Clínica de Neoplasias Litoral
🇧🇷Itajaí, Santa Catarina, Brazil
FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Onco
🇧🇷Santo Andre, SP, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
🇧🇷Santo André, SP, Brazil
Fundação Pio XII - Hospital de Câncer de Barretos
🇧🇷Barretos, SÃO Paulo, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷São José do Rio Preto, SÃO Paulo, Brazil
MHAT Uni Hospital OOD
🇧🇬Panagyurishte, Pazardzhik, Bulgaria
MHAT "Dr. Tota Venkova" AD
🇧🇬Gabrovo, Bulgaria
MHAT Central Onco Hospital OOD
🇧🇬Plovdiv, Bulgaria
Complex Oncology Center - Plovdiv EOOD
🇧🇬Plovdiv, Bulgaria
Medical Center Nadezhda Clinical EOOD
🇧🇬Sofia, Bulgaria
Acibadem City Clinic MHAT Tokuda
🇧🇬Sofia, Bulgaria
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
University Multiprofile Hospital for Active Treatment Sofiamed
🇧🇬Sofia, Bulgaria
Arthur J.E. Child Comprehensive Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
London Regional Cancer Program, London Health Sciences Centre
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Cancer Hospital Chinese Academy of Medical Science
🇨🇳Beijing, Beijing, China
Beijing Cancer hospital
🇨🇳Beijing, Beijing, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
The Sixth Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Affiliated Tumor Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
🇨🇳Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The Third Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Shengjing Hospital Of China Medical University
🇨🇳Shenyang, Liaoning, China
Shandong province cancer hospital
🇨🇳Jinan, Shandong, China
Shanghai Jiaotong University School of Medicine Ruijin Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai General Hospital
🇨🇳Shanghai, Shanghai, China
Sichuan Province Cancer Hospital
🇨🇳Chengdu, Sichuan, China
Yunnan Cancer Hospital(The Third Affiliated Hospital of Kunming Medical University)
🇨🇳Kunming, Yunnan, China
The second Affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Peking University First Hospital
🇨🇳Beijing, China
Tianjin Union Medical Center
🇨🇳Tianjin, China
St. Olavs hospital
🇳🇴Trondheim, Sør-trøndelag, Norway
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Fakultní nemocnice Brno Bohunice
🇨🇿Brno, Brno-město, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Hradec Králové, Czechia
Fakultni Thomayerova nemocnice
🇨🇿Prague, Praha 4, Czechia
Fakultni nemocnice Bulovka
🇨🇿Praha 8, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Aalborg Universitetshospital, Syd
🇩🇰Aalborg, Nordjylland, Denmark
Vejle Hospital-Sygehus Lillebaelt
🇩🇰Vejle, Syddanmark, Denmark
Vejle Sygehus
🇩🇰Vejle, Syddanmark, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Herlev and Gentofte Hospital
🇩🇰Herlev, Denmark
Odense University Hospital
🇩🇰Odense C, Denmark
Docrates Syöpäsairaala
🇫🇮Helsinki, Nyland, Finland
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Oulu University Hospital
🇫🇮Oulu, Finland
Satakunnan Keskussairaala
🇫🇮Pori, Finland
Tampereen yliopistollinen sairaala
🇫🇮Tampere, Finland
Turku University Hospital
🇫🇮Turku, Finland
Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie
🇩🇪Muenchen, Bayern, Germany
Institut für Klinisch Onkologische Forschung
🇩🇪Frankfurt, Hessen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
Radiologie Berlin
🇩🇪Berlin - Charlottenburg, Germany
Onkologische Schwerpunktpraxis Kurfuerstendamm
🇩🇪Berlin, Germany
Waage Apotheke
🇩🇪Berlin, Germany
HELIOS Klinikum Berlin Buch GmbH
🇩🇪Berlin, Germany
Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus
🇩🇪Dresden, Germany
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Facharztzentrum Eppendorf
🇩🇪Hamburg, Germany
ZytoService Deutschland GmbH, Standort-Hamburg-Jenfeld
🇩🇪Hamburg, Germany
Radiologie im Israelitischen Krankenhaus
🇩🇪Hamburg, Germany
Rajiv Gandhi Cancer Institute And Research Centre
🇮🇳New Delhi, Delhi, India
Tata Memorial Hospital
🇮🇳Mumbai, Maharashtra, India
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳Pune, Maharashtra, India
Sahyadri Speciality Hospital
🇮🇳Pune, Maharashtra, India
Bhakti Vedanta Hospital and Research Institute
🇮🇳Thane, Maharashtra, India
R K Birla Cancer Center, SMS Hospital
🇮🇳Jaipur, Rajasthan, India
Sawai Man Singh Medical College Hospital (SMS Hospital)
🇮🇳Jaipur, Rajasthan, India
Azienda Ospedaliera Universitaria di Cagliari - Presidio Policlinico Universitario "D.Casula"
🇮🇹Monserrato (CA), Cagliari, Italy
IRCCS Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milan, Milano, Italy
Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo IRCCS
🇮🇹Candiolo, Torino, Italy
Azienda Ospedaliero Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Torino, Italy
Fondazione Poliambulanza Istituto Ospedaliero
🇮🇹Brescia, Italy
Istituto Europeo di Oncologia IRCCS
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" di Napoli
🇮🇹Napoli, Italy
IRCCS Istituto Oncologico Veneto (IOV)
🇮🇹Padova, Italy
Azienda USL - IRCCS di Reggio Emilia - Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Chiba cancer center
🇯🇵Chiba-shi, Chiba, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Ishikawa, Japan
St. Marianna University Hospital
🇯🇵Kawasaki, Kanagawa, Japan
Kanagawa cancer center
🇯🇵Yokohama, Kanagawa, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya, Nagoya, Aichi, Japan
Osaka Prefectural Hospital Organization Osaka International Cancer Institute
🇯🇵Osaka-shi, Osaka, Japan
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
Osaka Medical and Pharmaceutical University Hospital
🇯🇵Takatsuki, Osaka, Japan
Saitama Medical University International Medical Center
🇯🇵Hidaka-city, Saitama, Japan
Saitama Prefectural Cancer Center
🇯🇵Ina-machi, Saitama, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi, Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Japanese Foundation for Cancer Research
🇯🇵Koto-ku, Tokyo, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
National Hospital Organization - Osaka National Hospital - Institute For Clinical Research
🇯🇵Osaka, Japan
Keio university hospital
🇯🇵Tokyo, Japan
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Taegu-kwangyǒkshi, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Accelerium, S. de R.L. de C.V.
🇲🇽Monterrey, Nuevo LEON, Mexico
Centro de Investigacion Clinica de Oaxaca
🇲🇽Oaxaca, Mexico
Catharina Ziekenhuis
🇳🇱Eindhoven, Noord-brabant, Netherlands
Oslo universitetssykehus, Radiumhospitalet
🇳🇴Oslo, Norway
Oslo Universitetssykehus Ullevål
🇳🇴Oslo, Norway
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
🇳🇱Amsterdam, Noord-holland, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
Sørlandet Sykehus Kristiansand
🇳🇴Kristiansand, Vest-agder, Norway
Przychodnia Lekarska KOMED
🇵🇱Konin, Wielkopolskie, Poland
Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
🇵🇱Brzozow, Poland
COPERNICUS PL sp. z. o. o. Wojewodzkie Centrum Onkologii w Gdansku Ambulatoryjna
🇵🇱Gdansk, Poland
COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii
🇵🇱Gdansk, Poland
Wojewodzki Szpital Specjalistyczny Nr 4 w Bytomiu Oddzial Onkologii
🇵🇱Bytom, Poland
Private Medical Institution "Euromedservice"
🇷🇺Pushkin, Saint-petersburg, Russian Federation
GBUZ
🇷🇺Chelyabinsk, Russian Federation
Kaluga Regional Clinical Oncology Center
🇷🇺Kaluga, Russian Federation
FSAEI HE I.M Sechenov First MSMU MoH Russia (Sechenovskiy University),
🇷🇺Moscow, Russian Federation
BHI of Omsk Region "Clinical Oncology Dispensary"
🇷🇺Omsk, Russian Federation
LLC "EuroCityClinic"
🇷🇺Saint Petersburg, Russian Federation
LLC "Medicina Severnoy Stolitsy"
🇷🇺Saint-Petersburg, Russian Federation
LLC "Severo-Zapadny Medical Center"
🇷🇺Saint-Petersburg, Russian Federation
Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg
🇷🇺Saint-Petersburg, Russian Federation
FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov
🇷🇺St. Petersburg, Russian Federation
SHI YR Regional Clinical Oncology Hospital
🇷🇺Yaroslavl, Russian Federation
Narodny Onkologicky Ustav
🇸🇰Bratislava, Slovakia
Ivano-Frankivsk National Medical University
🇺🇦Ivano-Frankivsk, Ukraine
Vychodoslovensky onkologicky ustav, a.s.
🇸🇰Kosice, Slovakia
Cancercare Rondebosch Oncology
🇿🇦Rondebosch, Cape Town, South Africa
Cancercare Langenhoven Drive Oncology Centre
🇿🇦Port Elizabeth, Eastern CAPE, South Africa
Wits Health Consortium (Pty) Ltd
🇿🇦Johannesburg, South Africa
Complejo Hospitalario Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruña, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
ICO L'Hospitalet (Hospital Duran i Reynals)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Karolinska Universitetssjukhuset Solna
🇸🇪Solna, Stockholms LÄN [se-01], Sweden
Akademiska sjukhuset
🇸🇪Uppsala, Uppsala LÄN [se-03], Sweden
Norrlands universitetssjukhus
🇸🇪Umeå, Västerbottens LÄN [se-24], Sweden
Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Västra Götalands LÄN [se14], Sweden
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng-Kung University Hospital
🇨🇳Tainan, Taiwan
Chi Mei Hospital, Liouying
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch
🇨🇳Taoyuan, Taiwan
Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
🇺🇦Dnipro, Ukraine
MNPE "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Regional Council"
🇺🇦Ivano-Frankivsk, Ukraine
Communal enterprise "Kryvyi Rih Oncology Dispensary" of Dnipropetrovsk Regional Council
🇺🇦Kryvyi Rih, Ukraine
Freeman Hospital
🇬🇧Newcastle upon Tyne, HIGH Heaton, United Kingdom
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, Surrey, United Kingdom
Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Hammersmith Hospital, Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Churchill Hospital - Oncology
🇬🇧Oxford, United Kingdom