Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-center, Open-label, Randomized, Phase 2 Clinical Trial Evaluating Safety and Efficacy of FOLFIRI With Either Panitumumab or Bevacizumab as Second-Line Treatment in Subjects With Metastatic Colorectal Cancer With Wild-type KRAS Tumors
Brief Summary: This is a multi-center, open-label, randomized, phase 2, two-arm clinical trial to be conducted in the United States. Approximately 210 eligible KRAS wild-type expressing metastatic colorectal cancer subjects who have failed first-line oxaliplatin-based chemotherapy (with at least 4 doses of oxaliplatin-based chemotherapy) with at least 4 doses of bevacizumab (failure is defined as toxicity due to oxaliplatin-based chemotherapy or progression of disease on first-line treatment) will be randomized in a 1:1 ratio to receive either a once-every-two-weeks (Q2W) FOLFIRI regimen plus panitumumab 6 mg/kg or a Q2W FOLFIRI regimen plus bevacizumab (either 5 mg/kg or 10 mg/kg, depending on physician choice and institutional standard of care).


Options:
A: MAIN ELIGIBILITY CRITERIA

* Histologically proven metastatic adenocarcinoma of colon or rectum
* Documented inoperable disease (i.e., not suitable for complete carcinological surgical resection)
* Measurable lesion as assessed by CT scan or MRI in at least one dimension (longest diameter to be recorded) ≥ 20 mm with conventional CT scan or ≥ 10 mm with spiral CT scan
* No previous therapy for metastatic disease
* No history or evidence upon physical examination of CNS disease (e.g., non-irradiated CNS metastasis, seizure not controlled with standard medical therapy, or history of stroke) unless adequately treated
* No exclusive bone metastasis
* ECOG performance status 0-2
* WBC ≥ 1,500/mm\^3
* Platelets ≥ 100,000/mm\^3
* Hemoglobin \> 9 g/dL (may be transfused to maintain or exceed this level)
* Proteinuria \< 2+ by dipstick OR ≤ 1 g of protein on 24-hr urine collection
* Bilirubin \< 1.5 times ULN
* Alkaline phosphatase \< 3 times ULN
* No peripheral sensory neuropathy
* Negative pregnancy test
* Fertile patients must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterilization)
* No peripheral neuropathy ≥ grade 1
* No clinically significant (i.e. active) cardiovascular disease
* No evidence of bleeding diathesis or coagulopathy
* No serious, non-healing wound, ulcer, or bone fracture
* No significant ophthalmologic abnormality
* More than 28 days since prior major surgical procedure or open biopsy
B: Inclusion Criteria:

* Man or woman at least 18 years old
* Diagnosis of metastatic colorectal cancer (mCRC)
* One and only one chemotherapy regimen for mCRC consisting of first-line 5-FU -based chemotherapy
* Radiologically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria during treatment or within 6 months of last dose of first-line chemotherapy
* At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST
* Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2
* Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyses
* Adequate hematologic, renal, and hepatic functions
* Negative pregnancy test within 72 hours of enrollment
* Other protocol-specified criteria may apply

Exclusion Criteria:

* History of or known presence of central nervous system (CNS) metastases
* History of another primary cancer within 5 years of randomization
* Prior irinotecan therapy
* Prior anti-epidermal growth factor receptor (EGFr) antibody therapy or treatment with small molecule EGFr inhibitors
* Any investigational agent or therapy within 30 days before randomization
* Known allergy or hypersensitivity to irinotecan, 5-FU or leucovorin
* History of interstitial lung disease or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
* Active inflammatory bowel disease or other bowel disease causing chronic diarrhea
* Known positive tests for human immunodefiency virus (HIV), hepatitis C viris (HCV), acute or chronic active hepatitis B virus (HBV)
* Major surgery within 28 days of randomization or minor surgical procedure within 14 days of randomization
* Pregnant or breast-feeding
* Man or woman of child-bearing potential not consenting to use adequate contraceptive methods or abstinence during the course of the study and for 6 months after last study drug administration (women) or 1 month after last study drug administration (men)
* Other protocol-specified criteria may apply
C: Inclusion Criteria: - Subject previously randomized to BSC in protocol 20020408 and subsequently determined to have progressive disease - ECOG performance status of 0, 1 or 2 - Adequate hematologic, renal and hepatic function Exclusion Criteria: - Myocardial infarction in time interval between completing 20020408 and enrollment in study - History or evidence of interstitial pneumonitis or pulmonary fibrosis - Prior anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules and biologics during the time interval between completing 20020408 protocol and enrollment in this study - Use of systemic chemotherapy or radiotherapy during the time interval between completing 20020408 protocol and enrollment in this study
D: Inclusion Criteria

* Diagnosis of metastatic adenocarcinoma of the colon or rectum that cannot, in the opinion of the investigator, be cured by surgical resection at the time of randomization
* Wild-type KRAS expressing mCRC from the primary tumor or metastasis.
* Failure of prior first-line oxaliplatin-based chemotherapy with bevacizumab (at least four therapeutic doses of oxaliplatin-based chemotherapy and bevacizumab) for mCRC.
* At least one uni-dimensionally measurable lesion per modified RECIST criteria.
* Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Man or woman 18 years of age or older
* Hematology, chemistry, coagution, metabolic functions within normal or protocol-defined limits

Exclusion Criteria

* Previous irinotecan, anti-EGFr therapy (eg, cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) or vaccine for the treatment of mCRC
* Radiotherapy ≤ 14 days before randomization
* Evidence of central nervous system (CNS) metastases
* Unresolved toxicities from prior anti-cancer therapy that, in the opinion of the investigator, precludes subject from participation
* History of other invasive primary cancer, except:
* Curatively resected or treated non-melanomatous skin cancer
* Curatively treated cervical carcinoma in situ
* Other primary solid tumor treated curatively and no treatment administered ≤ 2 years before randomization and, in the investigator's opinion, it is unlikely that there will be a recurrence ≤ 2 years post randomization

Medications

* C hronic daily treatment (as determined by the investigator) with aspirin (\> 325 mg/day) or non steroidal anti inflammatory agents known to inhibit platelet function
* Infection requiring a course of systemic anti-infectives that was completed ≤ 14 days before randomization (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection \[UTI\])
* Subjects concurrently receiving any investigational agent or therapy ≤ 30 days before randomization

General:

* Significant cardiovascular risk as defined by the protocol
* History of peripheral arterial ischemia ≤ 24 weeks before randomization (subjects with brief, reversible, exercise-induced claudication are eligible)
* History of visceral arterial ischemia ≤ 24 weeks before randomization
* Significant bleeding risk:
* Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days before randomization
* Anticipation of need for major surgical procedures during the course of the study
* C ore biopsy or other minor procedure, excluding placement of a vascular access device ≤ 7 days before randomization
* A ny significant bleeding that is not related to the primary colon tumor ≤ 24 weeks before randomization
* P re-existing bleeding diathesis or coagulopathy with the exception of well-controlled chronic anticoagulation therapy
* Serious or non-healing wounds, skin ulcers, or unhealed bone fractures
* Gastroduodenal ulcer(s) determined by endoscopy to be active or uncontrolled gastrointestinal ulcer ≤ 28 days before randomization
* History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest x-ray (CXR) or computed tomography (CT) scan
* Clinically significant ascites
* Subjects known to be human immunodeficiency virus (HIV) positive or known to have chronic or active hepatitis B or C infection
* Men and women of childbearing potential (women who are post-menopausal \< 52 weeks, not surgically sterilized, or not abstinent) who do not consent to use adequate contraception (according to institutional standard of care) during the course of the study and after the last date of receiving second-line treatment (24 weeks for women, 4 weeks for men)
* Women who test positive for serum or urine pregnancy test ≤ 72 hours before randomization or are breast-feeding
* Subjects allergic to any component that is part of the treatment regimen

Answer: D