Colorectal Cancer
Conditions
Brief summary
This open-label, randomized, multicenter, Phase 2 study will evaluate the safety and efficacy of MEHD7945A when combined with FOLFIRI (folinic acid \[leucovorin\], 5-fluorouracil \[5-FU\], and irinotecan) chemotherapy as compared to cetuximab plus FOLFIRI in participants with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type mCRC who have progressed after first-line oxaliplatin-containing chemotherapy for metastatic disease. Participants will be randomized to receive FOLFIRI chemotherapy plus either MEHD7945A or cetuximab. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Interventions
DRUG5-fluorouracil
Standard 5-fluorouracil (5-FU) chemotherapy (400 milligram per square meter \[mg/m\^2\] administered as intravenous bolus and then 5-FU 2400 mg/m\^2 administered as continuous intravenous infusion over 46 +/- 2 hours) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.
DRUGCetuximab
Cetuximab 400 mg/m\^2 intravenous infusion as a loading dose on Day 1 Cycle 1, followed by 250 mg/m\^2 intravenous infusion weekly until documented disease progression or unacceptable toxicity.
DRUGIrinotecan
Standard Irinotecan chemotherapy (180 milligram per square meter \[mg/m\^2\] administered as intravenous infusion over 60 +/- 30 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.
DRUGLeucovorin
Standard Leucovorin chemotherapy (400 mg/m\^2 \[racemic form\] or 200 mg/m\^2 \[L-isomer form\] administered by intravenous infusion over 120 +/- 10 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.
DRUGMEHD7945A
MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum, with KRAS wild-type status * Progressive disease on or after first-line oxaliplatin-containing regimen for mCRC; participants must have received oxaliplatin-containing chemotherapy for greater than or equal to (\>/=) 3 months; no more than one prior chemotherapy regimen for metastatic disease is allowed * Measurable disease per modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate hematologic and end-organ function
Exclusion criteria
* Prior treatment with irinotecan * Prior treatment with an investigational or approved human epidermal growth factor receptor (HER)-targeted agent * Last anti-tumor therapy within 4 weeks prior to Cycle 1, Day 1 * Leptomeningeal disease as the only manifestation of the current malignancy * Active infection requiring intravenous antibiotics * Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs * Current severe, uncontrolled systemic disease * Known human immunodeficiency virus (HIV) infection * Untreated/active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) * Pregnant or lactating women * Malignancies other than colorectal cancer within 5 years prior to randomization, except for adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria | approximately 2 year |
Secondary
| Measure | Time frame |
|---|---|
| Plasma Concentration of Irinotecan | Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4 |
| Number of Participants With Anti-MEHD7945A Antibodies | Pre-dose on Day 1 Cycles 1, 4, and 8; treatment completion visit (up to approximately 2 years) |
| Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria | approximately 2 year |
| Duration of Objective Response According to Modified RECIST v1.1 Criteria | approximately 2 year |
| Plasma Concentration of 5-Fluorouracil | Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4 |
| Number of Participants With Adverse Events | approximately 2 year |
| Maximum Observed Serum Concentration (Cmax) of MEHD7945A | Pre-dose and 30 minutes after end of infusion on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year) |
| Minimum Observed Serum Concentration (Cmin) of MEHD7945A | Pre-dose on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year) |
| Overall Survival (OS) | approximately 2 year |
Countries
Australia, Belgium, France, Germany, Italy, New Zealand, Romania, Spain, United Kingdom, United States
Outcome results
None listed