A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy
- Conditions
- Colorectal Neoplasms
- Interventions
- Registration Number
- NCT06750094
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 700
- Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease
- Be diagnosed to have KRAS, NRAS, and BRAF wild-type (WT) tumor as determined by local testing
- Must agree to the submission of fresh or archival tumor tissue post-progression from the most recent therapy, if clinically feasible
- Have measurable disease according to RECIST v1.1
- Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
- Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy
- Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
- Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: amivantamab, cetuximab or bevacizumab or any component of FOLFIRI
- Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status who has not received immunotherapy treatments
- Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor
- Has prior exposure to irinotecan, any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Amivantamab + FOLFIRI Amivantamab Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium \[folinic acid\] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm A: Amivantamab + FOLFIRI 5-fluorouracil Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium \[folinic acid\] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm A: Amivantamab + FOLFIRI Irinotecan Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium \[folinic acid\] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm B: Cetuximab or Bevacizumab + FOLFIRI Cetuximab Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm B: Cetuximab or Bevacizumab + FOLFIRI Bevacizumab Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm B: Cetuximab or Bevacizumab + FOLFIRI 5-fluorouracil Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm B: Cetuximab or Bevacizumab + FOLFIRI Leucovorin calcium/Levoleucovorin Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm B: Cetuximab or Bevacizumab + FOLFIRI Irinotecan Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met. Arm A: Amivantamab + FOLFIRI Leucovorin calcium/Levoleucovorin Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium \[folinic acid\] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Up to 2 years 1 month PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by BICR using response evaluation criteria in solid tumors (RECIST) version (v)1.1. Participants who have not progressed or have not died at the time of analysis will be censored at their last evaluable RECIST v1.1 assessment date.
Overall Survival (OS) Up to 4 years 4 months OS is defined as the time from the date of randomization to the date of participant's death due to any cause.
- Secondary Outcome Measures
Name Time Method Progression Free Survival After Subsequent Therapy (PFS2) Up to 4 years 4 months PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent systemic anticancer therapy, based on investigator assessment or death, whichever comes first.
Objective Response Rate as Assessed by Investigator Up to 4 years 4 months ORR is defined as the percentage of randomized participants achieving PR or CR, as assessed by investigator.
Objective Response Rate (ORR) as Assessed by BICR Up to 4 years 4 months ORR is defined as the percentage of randomized participants achieving partial response (PR) or complete response (CR), as determined by BICR using RECIST v1.1 criteria.
Progression Free Survival as Assessed by Investigator Up to 4 years 4 months PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by investigator.
Duration of Response (DoR) as Assessed by BICR Up to 4 years 4 months DoR is defined as time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR as assessed by BICR.
Duration of Response as Assessed by Investigator Up to 4 years 4 months DoR is defined as time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR as assessed by investigator.
Disease Control Rate (DCR) as Assessed by BICR Up to 4 years 4 months DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with a minimum duration of 7 weeks) as defined by BICR using RECIST v1.1.
Disease Control Rate as Assessed by Investigator Up to 4 years 4 months DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with a minimum duration of 7 weeks) as assessed by investigator.
Time to Treatment Failure Up to 4 years 4 months Time to treatment failure is defined as time from randomization to discontinuation of therapy for any reason including death, progression, toxicity, or initiation of new anticancer therapy.
Curative Resection (R0) Rate Up to 4 years 4 months Curative resection (R0) rate is defined as the percentage of randomized participants who underwent curative surgery.
Number of Participants with Adverse Events (AEs) by Severity Up to 4 years 4 months An AE is any untoward medical occurrence in a participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. by using standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; and Grade 5: Death related to AE.
Number of Participants with Abnormalities in Laboratory Values Up to 4 years 4 months Participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported.
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score From baseline up to 4 years 4 months The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptoms.
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30 Up to 4 years 4 months Time to worsening in symptoms and functioning as measured by EORTC QLQ-C30 score will be reported. The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptoms.
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C29) Score From baseline up to 4 years 4 months The EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms (gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image, weight, and anxiety) that are associated with colorectal cancer and its treatments. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." All scores are linearly converted into a scale from 0 to 100. Higher scores indicate greater functioning and more severe symptoms.
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C29 Score Up to 4 years 4 months Time to worsening in symptoms and functioning as measured by EORTC QLQ-CR29 will be reported. EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms (gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image, weight, and anxiety) that are associated with colorectal cancer and its treatments. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." All scores are linearly converted into a scale from 0 to 100. Higher scores indicate greater functioning and more severe symptoms. Change from baseline in the EORTC QLQ-CR29 score will be reported.
Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score Up to 4 years 4 months EORTC item 168 is a single item used to measure the overall impact of treatment side effects. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much. Higher scores indicates severe symptoms.
Trial Locations
- Locations (14)
Cancer and Blood Specialty Clinic
🇺🇸Los Alamitos, California, United States
Providence Medical Foundation
🇺🇸Santa Rosa, California, United States
Concord Hospital
🇦🇺Concord, Australia
Warringal Private Hospital
🇦🇺Heidelberg, Australia
Queen Elizabeth Hospital
🇦🇺South Woodville, Australia
MedStar Franklin Square Medical Center
🇺🇸Baltimore, Maryland, United States
Western Health Sunshine Hospital
🇦🇺St Albans, Australia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
Pan American Center for Oncology Trials LLC
🇵🇷Barrio Monacillos, Puerto Rico
Kaohsiung Medical University Chung Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan