Randomized, Active-Controlled, Open-Label Phase 2 Study of CS-7017 in Combination With FOLFIRI in Subjects With Metastatic Colorectal Cancer Who Failed First-Line Therapy
Overview
- Phase
- Phase 2
- Intervention
- irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)
- Conditions
- Colorectal Cancer
- Sponsor
- Daiichi Sankyo
- Enrollment
- 100
- Locations
- 17
- Primary Endpoint
- Percentage of Participants With Progression-Free Survival at 16 Weeks After Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This phase 2, randomized, active-controlled, open-label, parallel group, multicenter study will be conducted at up to 18 study centers in the US, Central America, and South America. Adult subjects with metastatic colorectal cancer (CRC) who failed first-line chemotherapy will participate in the study, which will be conducted on an outpatient basis. It is anticipated that 100 subjects will be enrolled to obtain approximately 90 evaluable subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Metastatic CRC that has progressed following first-line therapy.
- •Measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\], Version 1.
- •Male or female ≥ 18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, Version 3.0, grade ≤
- •Adequate organ and bone marrow function as evidenced by:
- •Hemoglobin ≥ 9 g/dL (transfusion and/or growth factor support allowed)
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
- •Platelet count ≥ 100 x 10\^9/L
- •Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) or creatinine clearance ≥ 60 mL/min
Exclusion Criteria
- •First-line treatment with an irinotecan-based regimen (eg, FOLFIRI).
- •Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study.
- •Treatment with chemotherapy, other thiazolidinediones (TZD), RT, surgery, immunotherapy, biological therapy, or any investigational anticancer agent within 4 weeks before start of study treatment.
- •History of any of the following conditions within 6 months before initiating study treatment:
- •Diabetes mellitus requiring treatment with insulin or TZD agents
- •Myocardial infarction with significant impairment of cardiac function (eg, ejection fraction ≤ 50%)
- •Severe/unstable angina pectoris
- •Coronary/peripheral artery bypass graft
- •New York Heart Association (NYHA) class III or IV congestive heart failure
- •Malabsorption syndrome, chronic diarrhea (lasting \> 4 weeks), inflammatory bowel disease, or partial bowel obstruction.
Arms & Interventions
FOLFIRI
Participants who received irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI). FOLFIRI was administered by intravenous (IV) injection once every 2 weeks. The FOLFIRI regimen consisted of: * Irinotecan, 180 mg/m\^2 IV infusion over 30 to 120 minutes * Leucovorin, 400 mg/m\^2 IV infusion to match the duration of the irinotecan infusion * 5-FU, 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46 to 48 hours continuous infusion)
Intervention: irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)
CS7017+FOLFIRI
Participants who received CS7017 plus irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI). Two CS-7017 tablets were administered by mouth (PO) twice a day (BID) every 12 hours. FOLFIRI was administered IV once every 2 weeks. The FOLFIRI regimen consisted of: * Irinotecan, 180 mg/m\^2 IV infusion over 30 to 120 minutes * Leucovorin, 400 mg/m\^2 IV infusion to match the duration of the irinotecan infusion * 5-FU, 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46 to 48 hours continuous infusion)
Intervention: CS7017
CS7017+FOLFIRI
Participants who received CS7017 plus irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI). Two CS-7017 tablets were administered by mouth (PO) twice a day (BID) every 12 hours. FOLFIRI was administered IV once every 2 weeks. The FOLFIRI regimen consisted of: * Irinotecan, 180 mg/m\^2 IV infusion over 30 to 120 minutes * Leucovorin, 400 mg/m\^2 IV infusion to match the duration of the irinotecan infusion * 5-FU, 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46 to 48 hours continuous infusion)
Intervention: irinotecan, leucovorin, and 5-fluorouracil (5-FU) (FOLFIRI)
Outcomes
Primary Outcomes
Percentage of Participants With Progression-Free Survival at 16 Weeks After Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer
Time Frame: Baseline to 16 weeks postdose
Progression-free survival (PFS) was defined as the time from randomization until the first objective evidence of disease progression or death from any cause.
Secondary Outcomes
- Median Overall Progression-Free Survival: Sensitivity Analysis Including Clinical Progression After Administration of CS-7017 and Irinotecan, Leucovorin, and 5-Fluorouracil After Failure of First-line Therapy of Metastatic Colorectal Cancer(Baseline to approximately 3 years postdose)
- Median Overall Progression-Free Survival Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer(Baseline to approximately 3 years postdose)
- Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer(Baseline to approximately 3 years postdose)
- Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer(Baseline to 30 days post last dose, up to approximately 3 years)