Cancer, Carcinoma, Colon Cancer, Colorectal Cancer, Gastrointestinal Cancer, Metastases, Metastatic Cancer, Metastatic Colorectal Cancer, Oncology, Rectal Cancer
Conditions
Keywords
Metastatic Colorectal Cancer, colorectal cancer, colon cancer
Brief summary
This clinical trial will compare the efficacy and safety of the combination of AMG 386 and FOLFIRI with FOLFIRI alone in second line treatment of metastatic colorectal cancer.
Interventions
DRUGAMG 386
AMG 386 (10 mg/kg QW) will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.
DRUGAMG 386 Placebo
AMG 386 placebo QW will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.
DRUGFOLFIRI
Administration of FOLFIRI chemotherapy will commence on day 1 of each dosing week following the administration of AMG 386. FOLFIRI Q2W regimen: irinotecan 180 mg/m2 IV over 90 (+-15) minutes on Day 1, leucovorin 400 mg/m2 IV over 2 hrs on Day 1, 5 FU 400mg/m2 IV bolus, followed by 2400 mg/m2 continuous IV infusion over 46 hrs +- 2 hours. FOLFIRI will be administered until disease progression, FOLFIRI intolerability, death, or study withdrawal by the subject, investigator, or sponsor, whichever occurs earliest.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed adenocarcinoma of the colon or rectum in patients who are presenting with metastatic disease * One and only one prior chemotherapy regimen for metastatic disease consisting of the combination of a fluoropyrimidine-based chemotherapy and an oxaliplatin-based chemotherapy. Prior adjuvant chemotherapy used prior to the onset of metastatic disease is permitted * At least one uni dimensionally measurable lesion per modified RECIST criteria. All sites of disease must be evaluated \<= 28 days before randomization * Radiographically documented disease progression per modified RECIST criteria either while receiving or \<= 6 months after the last dose of prior chemotherapy regimen for metastatic disease * ECOG performance status of 0 or 1 * Man or woman \>= 18 years of age * Adequate end organ assessments by laboratory studies (hematological and chemistries) * Life expectancy \>= 3 months
Exclusion criteria
* Exclude subjects with a history of prior malignancy, except: * Malignancy treated with curative intent and with no known active disease present for \>= 3 years before enrollment and felt to be at low risk for recurrence by treating physician * Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease * Adequately treated cervical carcinoma in situ without evidence of disease * Prostatic intraepithelial neoplasia without evidence of prostate cancer * Prior irinotecan therapy * Systemic chemotherapy, hormonal therapy, or immunotherapy \<= 21 days prior to randomization * Experimental or approved proteins/antibodies (eg, bevacizumab) \<= 30 days prior to randomization * Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent * Known allergy or hypersensitivity to irinotecan, 5 FU (known dihydropyrimidine dehydrogenase deficiency) or leucovorin * Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as \>= CTC grade 2 \[CTCAE version 3.0\])
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To estimate the treatment effect as measured by progression free survival (PFS) in subjects treated with AMG 386 + FOLFIRI relative to subjects treated with FOLFIRI + placebo. | The time frame will be event driven and will occur when 100 subjects have experienced a PFS event (radiographic disease progression or death). |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate other measures of efficacy or clinical response including objective response rate (ORR), duration of response (DOR), overall survival (OS) in subjects treated with AMG 386 + FOLFIRI relative to subjects treated with FOLFIRI + placebo | Treatment phase or until disease progression |
| To evaluate progression free survival and measures of efficacy by KRAS status | Treatment phase |
| To evaluate patient reported outcomes (PROs), relative dose intensity, incidence of anti AMG 386 antibody formation, pharmacokinetics of AMG 386 (Cmax and AUC) and safety (incidence of AEs and significant laboratory changes) | Throughout study |
Outcome results
None listed