Patient case: 54-year-old female with Breast cancer. Genetic variant: PTEN Loss. Other conditions: Congestive Heart Failure.

Clinical trial: Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study

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.

Detailed description: 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: 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

Relevance to patient case: not relevant