A Safety and Efficacy Study of CC-90011 in Participants With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas
- Conditions
- NeoplasmsLymphoma, Non-Hodgkin
- Interventions
- Registration Number
- NCT02875223
- Lead Sponsor
- Celgene
- Brief Summary
Study CC-90011-ST-001 is an open-label, Phase 1, dose escalation and expansion, First-In-Human (FIH) clinical study of CC-90011 in subjects with advanced unresectable solid tumors (enriched for grade 2 NENs, grade 2 NETs and NECs) and R/R NHL (MZL, including extranodal MZL \[EMZL\], splenic MZL \[SMZL\], nodal MZL \[NMZL\], and histologic transformation of MZL). The dose escalation part (Part A) of the study will explore escalating oral doses of CC-90011 to estimate the maximum tolerated dose (MTD) of CC-90011. The expansion part (Part B) will further evaluate the safety and efficacy of CC-90011 administered at or below the MTD in 3 selected expansion cohorts of approximately 10-20 evaluable subjects each, in order to further define the RP2D.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 75
- Advanced or unresectable solid tumors including those who have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy or for whom no other approved conventional therapy exists
- Eastern Cooperative Oncology Group Performance Status of 0 to 1
- Prior autologous stem cell transplant ≤ 3 months before first dose or those who have not recovered
- Symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and gastrointestinal tract hemorrhages
- Impaired cardiac function or clinically significant cardiac diseases
- Poor bone marrow reserve as assessed by Investigator
Refer to protocol defined exclusion criteria for parts C and D. Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CC-90011 and Rifampicin CC-90011 - CC-90011 and Itraconazole CC-90011 - CC-90011 and Rifampicin Rifampicin - CC-90011 and Itraconazole Itraconazole -
- Primary Outcome Measures
Name Time Method Part A - Number of Participants With Dose Limiting Toxicities (DLTs) Cycle 1 (Each cycle is of 28 days) Dose-limiting toxicities (DLTs) during dose escalation are defined as follows, occurring within the Cycle 1 (28 days) DLT assessment period, unless clearly unrelated to CC-90011: Any Grade 4 non-hematologic toxicity; any non-hematologic toxicity Grade ≥ 3 except Grade 3 diarrhea, nausea, or vomiting of ≤ 3 days duration, Grade 3 rash resolving to Grade ≤ 2 within 7 days without recurrence, and Grade 3 fatigue resolving to Grade ≤ 2 within 7 days without recurrence. Hematological toxicities include febrile neutropenia, Grade 4 neutropenia \> 7 days, Grade 4 thrombocytopenia \> 7 days, or Grade ≥ 3 thrombocytopenia with significant bleeding. Any AE necessitating dose reduction during Cycle 1, or any other toxicity deemed dose-limiting by the safety committee. The MTD is the highest dose at which less than 33% of the population treated with CC-90011 suffer a DLT in the first cycle and at least 6 evaluable participants have been treated at this dose.
Part A - Maximum Tolerated Dose (MTDs) Cycle 1 (Each cycle is of 28 days) The MTD is the highest dose at which less than 33% of the population treated with CC-90011 suffer a DLT in the first cycle and at least 6 evaluable participants have been treated at this dose. Dose-limiting toxicities (DLTs) during dose escalation are defined as follows, occurring within the Cycle 1 (28 days) DLT assessment period, unless clearly unrelated to CC-90011: Any Grade 4 non-hematologic toxicity; any non-hematologic toxicity Grade ≥ 3 except Grade 3 diarrhea, nausea, or vomiting of ≤ 3 days duration, Grade 3 rash resolving to Grade ≤ 2 within 7 days without recurrence, and Grade 3 fatigue resolving to Grade ≤ 2 within 7 days without recurrence. Hematological toxicities include febrile neutropenia, Grade 4 neutropenia \> 7 days, Grade 4 thrombocytopenia \> 7 days, or Grade ≥ 3 thrombocytopenia with significant bleeding. Any AE necessitating dose reduction during Cycle 1, or any other toxicity deemed dose-limiting by the safety committee.
- Secondary Outcome Measures
Name Time Method Part A - Clinical Benefit Rate (CBR) as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) From first dose (Day 1) till disease progression or death due to any cause (up to 803 days) The Clinical benefit rate (CBR) is defined as percentage of participants with tumor responses (as assessed by the Investigators) of CR, PR and durable SD (SD of ≥ 4 months duration). Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part A - Objective Response Rate as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) From first dose (Day 1) untill disease progression or death due to any cause (up to 803 days) The Objective Response Rate (ORR) is defined as the percentage of participants whose best response is CR or PR. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part A - Duration of Response (DoR) Based on Confirmed Responses From first dose (Day 1) until disease progression or death due to any cause (up to 803 days) Duration of response is measured from the time when criteria for CR/PR are first met (whichever is first recorded) until the first date at which progressive disease is objectively documented. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part A - Progression-Free Survival (PFS) From first dose (Day 1) until disease progression or death due to any cause (up to 803 days) Progression-Free Survival (PFS) is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause based on Kaplan-Meier methodology. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part A - Overall Survival (OS) From first dose (Day 1) until death due to any cause (up to 803 days) Overall Survival (OS) is defined as the time from the first dose of study drug to death due to any cause based on Kaplan-Meier methodology.
Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) Blood samples were collected to assess Cmax. Prespecified to be reported for Part A only.
Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) Blood samples were collected to assess AUCt. Prespecified to be reported for Part A only.
Part A - Time to Cmax (Tmax) of CC-90011 Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) Blood samples were collected to assess Tmax. Prespecified to be reported for Part A only.
Part A - Half-life (t1/2) of CC-90011 Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) Blood samples were collected to assess CL/F. Prespecified to be reported for Part A only.
Part A - Apparent Clearance (CL/F) of CC-90011 Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) Blood samples were collected to assess CL/F. Prespecified to be reported for Part A only.
Part A- Volume of Distribution (Vz/F) of CC-90011 Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) Blood samples were collected to assess Vz/F. Prespecified to be reported for Part A only.
Part B - Clinical Benefit Rate (CBR) as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) From first dose (Day 1) until disease progression or death due to any cause (up to 720 days) The Clinical Benefit Rate (CBR) is defined as tumor responses (as assessed by the Investigators) of CR, PR and durable SD (SD of ≥ 4 months duration). Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) From first dose (Day 1) till disease progression or death due to any cause (up to 720 days) The Objective Response Rate (ORR) is defined as the percent of participants whose best response is CR or PR. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part B - Duration of Response (DoR) From first dose (Day 1) until disease progression or death due to any cause (up to 720 days) Duration of response is measured from the time when criteria for CR/PR are first met (whichever is first recorded) until the first date at which progressive disease is objectively documented. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part B - Progression Free Survival (PFS) From first dose (Day 1) until disease progression or death due to any cause (up to 720 days) Progression-Free Survival (PFS) is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause based on Kaplan-Meier methodology Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Part B - Overall Survival (OS) From first dose (Day 1) until death due to any cause (up to 720 days) Overall Survival (OS) is defined as the time from the first dose of study drug to death due to any cause based on Kaplan-Meier methodology.
Trial Locations
- Locations (15)
Local Institution - 201
🇮🇹Milano, Italy
Local Institution - 500
🇯🇵Kashiwa, Japan
Local Institution - 501
🇯🇵Chuo-ku, Tokyo, Japan
Local Institution - 502
🇯🇵Koto-Ku, Tokyo, Japan
Local Institution - 101
🇫🇷Dijon, France
Local Institution - 100
🇫🇷Villejuif Cedex, France
Local Institution - 102
🇫🇷Marseille Cedex 9, France
Local Institution - 202
🇮🇹Milano, Italy
Local Institution - 200
🇮🇹Bologna, Italy
Local Institution - 402
🇪🇸Madrid, Spain
Local Institution - 400
🇪🇸Barcelona, Spain
Local Institution - 404
🇪🇸Madrid, Spain
Local Institution - 401
🇪🇸Santander, Spain
Local Institution - 300
🇬🇧London, United Kingdom
Local Institution - 301
🇬🇧Newcastle Upon Tyne, United Kingdom