A Phase 2 Study of Panitumumab Plus Irinotecan Followed by Panitumumab PlusAMG 479 in Subjects With Metastatic Colorectal Carcinoma Expressing Wild Type KRAS and Refractory to Oxaliplatin- or Irinotecan- and Oxaliplatin-containing Regimens to Evaluate Mechanisms of Acquired Resistance to Panitumumab

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 76

Inclusion Criteria

• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
• Subjects with wild-type KRAS tumor status confirmed by central laboratory assessment
• Radiographic evidence of disease progression while on or = 6 months after treatment with irinotecan- and oxaliplatin- or oxaliplatin-based chemotherapy for mCRC
• Radiographic measurement of tumor burden done within 28 days prior to Day 1 (start of treatment with investigational product)
• At least 1 uni-dimensionally measurable lesion = 20 mm using conventional CT or MRI or = 10 mm by spiral CT 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
• At least 1 tumor (metastatic lesion or unresected primary tumor) that is amenable to core needle biopsy, as determined by the clinician who will perform the biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix E)
• Male or female = 18 years of age at the time of informed consent
• Willing to undergo two core biopsy procedures of tumors (metastasis or unresected primary)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• History of prior or concurrent central nervous system (CNS) metastases
• Prior treatment with anti-EGFR antibodies (eg, panitumumab, cetuximab) or EGFR small molecule inhibitors (eg, erlotinib, gefitinib)
• Prior treatment with monoclonal antibodies directed against IGF-1R
• Use of systemic chemotherapy and radiotherapy = 21 days before enrollment
• Use of any antibody therapy (eg, bevacizumab) = 42 days before enrollment
• Use of anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules = 30 days before enrollment
• Known UGT1A1 polymorphisms predisposing to increased irinotecan toxicity
• History of irinotecan intolerance that may interfere with planned treatment
• History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan
• Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active 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 diathesis) or history of any medical condition that may interfere with the interpretation of the study results
• Major surgical procedure = 28 days before enrollment or minor surgical procedure = 14 days before enrollment. Subjects must have recovered from surgery related toxicities.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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