Please select the eligibility criteria that correspond to the clinical trial below.
Title: Multicenter Randomized Trial Evaluating FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment of Metastatic Colorectal Cancer.
Brief Summary: The FIRE-3 trial is a multicenter randomized phase III trial investigating 5-FU, folinic acid and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment of metastatic colorectal cancer. Planned accrual is 284 evaluable patients per treatment arm. The primary study endpoint is objective response rate. Secondary endpoints are median progression free survival, median overall survival, safety, and secondary resection rate.


Options:
A: Inclusion Criteria:

* Locally advanced Stage IIIB not amenable to local therapy or Stage IV (metastatic) NSCLC with adenocarcinoma histology.
* Never smokers or light ex-smokers.(ceased smoking at least 15 years before Day 1 of study treatment and 10 pack-years or fewer)

Exclusion Criteria:

* Had prior chemotherapy, biological (including targeted therapies such as EGFR and vascular epidermal growth factor (VEGF) inhibitors) or immunological therapy.
* Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline.
B: 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
C: Inclusion Criteria:

* KRAS-Wildtype status
* Histologically confirmed adenocarcinoma of the colon or rectum.
* Stage IV disease.
* ECOG 0-2.
* Patients considered suitable for application of chemotherapy.
* Age 18 - 75 years.
* In- or outpatient treatment.
* Estimated life expectancy \> 3 months.
* Measurable index lesion according to RECIST criteria. Evaluation of tumor manifestations ≤ 2 weeks prior to treatment start.
* Effective contraception.
* Adequate hematologic function: leukocytes \>= 3000/µl, neutrophils \>= 1500/µl, platelets \>= 100.000/µ, and hemoglobin \>= 9g/dl.
* Bilirubin \<= 1,5x upper limit of normal (ULN).
* ALAT and ASAT \<= 2,5x ULN, in case of liver metastases \<= 5x ULN.
* Serum creatinine \<= 1,5x ULN.
* No operations within 4 weeks prior to treatment start. No cytologic biopsies within 1 week prior to treatment start. Operation sequels need to be completely healed. Major operations must not be expected at time of study begin, except for potential secondary resection of liver metastases. In case of secondary resection of liver metastases, bevacizumab must be discontinued 6-8 weeks prior to surgery.
* No relevant toxicities due to prior medical treatment at time of study entry.

Exclusion Criteria:

* KRAS-Mutation of the tumor
* Prior treatment directed against the epidermal growth factor receptor (EGFR).
* Prior treatment with bevacizumab.
* Prior chemotherapy for colorectal cancer, except for adjuvant chemotherapy dating back \> 6 months prior to study entry.
* Experimental medical treatment within 30 days prior to study entry.
* Known hypersensitivity reaction to any study medication.
* Pregnant or breast feeding women (pregnancy needs to be excluded by testing of beta-HCG).
* Known or suspected cerebral metastases.
* Clinically significant coronary heart disease, myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia.
* Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhea.
* Symptomatic peritoneal carcinosis.
* Severe chronic wounds, ulcera or bone fracture.
* Uncontrolled hypertension.
* Severe proteinuria (nephrotic syndrome).
* Arterial thromboembolic events or hemorrhage within 6 months prior to study entry (except tumor bleeding surgically treated by tumor resection).
* Bleeding diatheses or coagulopathy.
* Full dose anticoagulation.
* Known DPD-deficiency (special screening not required).
* Known glucuronidation-deficiency (special screening not required).
* Medical history of other malignant disease within 5 years prior to study entry, except for basalioma, and in-situ cervical carcinoma if treated with curative intent.
* Known alcohol or drug abuse.
* Medical or psychiatric condition which contradicts participation of study.
* Limited legal capacity.
D: 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

Answer: C