conatumumab/panitumumab combination metastatic colorectal cancer study

Conditions: Colon Cancer; Colorectal Cancer; Rectal Cancer; Metastatic Colorectal Cancer; Oncology

Summary: this is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with metastatic colorectal cancer.

this is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with metastatic colorectal cancer. the objective for part 1 is to identify a tolerable dose of conatumumab in combination with panitumumab based on the incidence of dose-limiting toxicities in patients with metastatic colorectal cancer. the objective for part 2 is to evaluate the objective response rate stratified by kirsten rat sarcoma virus oncogene (kras) status (wild-type versus mutant) in patients with metastatic colorectal cancer treated with the combination of panitumumab and conatumumab (tolerable dose identified in part 1).

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum * radiographically documented disease progression per modified response evaluation criteria in solid tumors (recist) during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for metastatic colorectal cancer. progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment. * at least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified recist. lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. all sites of disease must be evaluated. * eastern cooperative oncology group (ecog) performance status of 0 or 1 * available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory * man or woman ≥ 18 years of age at the time of enrollment * hematologic function within the following limits: * absolute neutrophil count (anc) \> 1.0 x 10\^9 cells/l * platelets ≥ 100 x 10\^9/l * renal function within the following limits: * creatinine \< 2.0 mg/dl * hepatic function within the following limits: * aspartate aminotransferase (ast) ≤ 2.5 x upper limit of normal (uln) (≤ 5 x uln if liver metastases) * alanine aminotransferase (alt) ≤ 2.5 x uln (≤ 5 x uln if liver metastases) * bilirubin ≤ 2 x uln * metabolic function within the following limits: * amylase ≤ 2 x uln * lipase ≤ 2 x uln * magnesium ≥ lower limit of normal * negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only) * must have received 1, 2, or 3 prior chemotherapy regimens for metastatic colorectal cancer * competent to comprehend, sign, and date the independent ethics committee/institutional review board (iec/irb) approved written informed consent exclusion criteria: * history of other primary cancer, unless: * curatively resected non-melanomatous skin cancer * curatively treated cervical carcinoma in situ * other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment * prior treatment with anti-epidermal growth factor receptor (egfr) inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment * use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment * use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment * use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment * any investigational agent or therapy ≤ 30 days before enrollment * known allergy or hypersensitivity to any component of panitumumab and/or amg 655 * history of or known presence of central nervous system (cns) metastases * history of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (ct) scan * clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment * active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ common terminology criteria for adverse events \[ctcae\] grade 2 \[ctcae version 3.0\]) * known positive test for human immunodeficiency virus (hiv) infection, hepatitis c virus, acute or chronic hepatitis b infection * any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion) * any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results * major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. patients must have recovered from surgery related toxicities. * other investigational procedures are excluded * patient is currently pregnant or breast feeding * man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence. * previously enrolled into this study * patient unwilling or unable to comply with study requirements