Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III Study of an Optimized Chemotherapy Followed by Maintenance With Bevacizumab Strategy With or Without Erlotinib in Unresectable Metastatic Colorectal Cancer. DREAM OPTIMOX 3. C04-2
Brief Summary: PURPOSE: This randomized phase III trial is studying maintenance therapy with bevacizumab alone after an induction therapy combining bevacizumab+chemotherapy to see how well they work compared to maintenance therapy with bevacizumab+erlotinib alone after an induction therapy combining bevacizumab+chemotherapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.


Options:
A: Inclusion Criteria:

* Histological proof of colorectal cancer
* Initially unresectable metastases confined to the liver according to CT scan, obtained ≤3 weeks prior to registration. Unresectability should be confirmed by the liver expertpanel. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible
* Known mutation status of RAS and BRAF
* WHO performance status 0-1 (Karnofsky performance status ≥ 70)
* Age ≥ 18 years
* No contraindications for liver surgery
* In case of primary tumor in situ: tumor should be resectable
* In case of resected primary tumor: adequate recovery from surgery
* Adequate organ functions, as determined by normal bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, ≥ 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 5x ULN)
* Life expectancy \> 12 weeks
* Expected adequacy of follow-up
* Written informed consent

Exclusion Criteria:

* Extrahepatic metastases, with the exception of small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases
* Unresectable primary tumor
* Serious comorbidity or any other condition preventing the safe administration of study treatment (including both systemic treatment and surgery)
* Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation
* Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs
* Previous systemic treatment for metastatic disease; previous adjuvant treatment is allowed if completed ≥ 6 months prior to randomisation
* Previous surgery for metastatic disease
* Previous intolerance of study drugs in the adjuvant setting
* Pregnant or lactating women
* Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin, or second primary colorectal cancer.
* Any concomitant experimental treatment.
B: 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
C: Inclusion Criteria:

* Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in patients with unresectable metastatic (M1) disease
* Patients with at least 1 uni-dimensionally measurable lesion of at least 10 mm per modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
* Wild-type KRAS tumor status confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method
* Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
* Men or women 18 years of age or older
* Adequate hematologic, renal, hepatic, metabolic, and coagulation function

Exclusion Criteria:

* History of prior or concurrent central nervous system (CNS) metastases
* Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma
* Clinically significant cardiac disease
* Clinically significant peripheral sensory neuropathy
* Active inflammatory bowel disease
* Recent gastroduodenal ulcer to be active or uncontrolled
* History of interstitial lung disease
* Recent pulmonary embolism, deep vein thrombosis, or other significant venous event
* Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy
* Recent major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery.
D: Inclusion Criteria:

* Pathologic diagnosis of colorectal adenocarcinoma (diagnostic tissue obtained by tissue biopsy)
* Metastatic colorectal carcinoma
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Documented evidence of disease progression during, or following treatment, with fluoropyrimidine, irinotecan and oxaliplatin chemotherapy for metastatic colorectal cancer
* Radiographic documentation of disease progression during or within 6 months following the most recent chemotherapy regimen
* Unidimensionally measurable disease
* Tumor expressing epidermal growth factor receptor (EGFr) by immunohistochemistry
* At least 2 but not more than 3 prior chemotherapy regimens for colorectal cancer
* Adequate hematologic, renal and hepatic function

Exclusion Criteria:

* Symptomatic brain metastases requiring treatment
* History or evidence of interstitial pneumonitis or pulmonary fibrosis
* Use of systemic chemotherapy or radiotherapy within 30 days prior to enrollment
* Prior epidermal growth factor receptor (EGFr) targeting therapies
* Prior anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules and biologics of short (less than a week) serum half life within 30 days before enrollment, or prior experimental or approved proteins within 3 months before enrollment.

Answer: B