Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Trial of Treatment Strategy for Chemotherapy in Colorectal Cancer, FFCD 2000-05
Brief Summary: The standard treatment of metastatic colorectal cancer is based on systemic chemotherapy. Several effective drugs are currently available and can be administered either sequentially or in combination. Most patients receive 2 or 3 lines of chemotherapy. The aim of this randomized trial is to evaluate the potential benefit of a bitherapy with 5-fluorouracil (5-FU) and oxaliplatin as first line chemotherapy compared with a sequential chemotherapy with 5-FU alone as first line chemotherapy followed by the combination of 5-FU with oxaliplatin in case of progressive disease, in terms of progression-free survival and overall survival in patients with advanced colorectal cancer.


Options:
A: Inclusion Criteria:

* Histological or cytological documentation of adenocarcinoma of the colon or rectum
* Progression during or within 3 months following the last administration of approved standard therapies. Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy
* Patients with measurable or non measurable disease
* Eastern Cooperative Oncology Group (ECOG) Performance Status of \</= 1
* Life expectancy of at least 3 months
* Adequate bone marrow, liver and renal function

Exclusion Criteria:

* Unstable/uncontrolled cardiac disease
* History of arterial or venous thrombotic or embolic events
* Symptomatic metastatic brain or meningeal tumors
* Patients with evidence or history of bleeding diathesis
* Interstitial lung disease - Persistent proteinuria \>/= grade 3
* Unresolved toxicity \> grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity \</= Grade 2
B: 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.
C: Inclusion Criteria:

* Histologically confirmed metastatic colorectal adenocarcinoma
* Unresectable metastasis
* Bidimensionally measurable disease (World Health Organization \[WHO\] criteria)
* WHO performance status of 2 or less
* Adequate hematologic functions (neutrophil count, at least 1500 per cubic millimeter; and platelet count, at least 100,000 per cubic millimetre)
* Adequate renal function (serum creatinine, less than 125 micromol per liter)
* Adequate liver function (bilirubin, not more than 5 times the upper limit of normal)
* No previous chemotherapy other than previous adjuvant chemotherapy or concomitant chemoradiotherapy with 5-fluorouracil and leucovorin for the treatment of the primary tumor completed at least 6 months before inclusion
* Signed written inform consent
* Quality of life questionnaire (QLQ C-30) filled out

Exclusion Criteria:

* Pregnant or breast - feeding women
* Impossibility of regular follow-up for psychological, social or geographical reason
* Severe cardiac, respiratory, renal or hepatic failure
* Active coronary heart disease
* Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study
* Central nervous system metastases
* Past history of second malignancies
* Another investigational drug
* Chronic inflammatory bowel disease
* Previous chemotherapy with irinotecan or oxaliplatin based regimens
D: Inclusion Criteria:

* Histologically or cytologically confirmed colorectal cancer, excluding primary tumors of appendiceal origin (participants are eligible to enroll irrespective of KRAS mutation status)
* Confirmed metastatic colorectal cancer (Stage IV)
* The participant has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and, a) Experienced radiographic disease progression during first-line therapy, or b) Experienced radiographic disease progression ≤6 months after the last dose of first-line therapy, or c) Discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression ≤6 months after the last dose of first-line therapy. Note that a participant must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy; in addition, a participant must have received at least 1 cycle of first-line therapy that included bevacizumab, oxaliplatin and a fluoropyrimidine in the same cycle. Note that a participant must not have received more than 2 different fluoropyrimidines as part of a first-line regimen; disease progression is not an acceptable reason for discontinuing 1 fluoropyrimidine and starting a second fluoropyrimidine
* Receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted). For participants with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen. Note that rechallenge with oxaliplatin is permitted and will be considered part of the first-line regimen for metastatic disease, both initial oxaliplatin treatment and subsequent rechallenge are considered as 1 regimen
* Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
* Adequate hematologic, renal and hepatic function
* Adequate coagulation function \[International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x upper limit of normal (ULN)). Participants on full-dose anticoagulation must be on a stable dose of anticoagulant therapy and if on oral anticoagulation, must have an INR ≤3 and have no clinically significant active bleeding or pathological condition that carries a high risk of bleeding
* Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available
* Ability to provide signed informed consent

Exclusion Criteria:

* Receipt of bevacizumab ≤28 days prior to randomization
* Receipt of any investigational therapy for non-oncology clinical indication ≤28 days prior to randomization
* Receipt of any previous systemic therapy, other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine, for first-line treatment of metastatic colorectal cancer
* Known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression (currently or in the past)
* Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to, myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤12 months prior to randomization
* Pregnant (confirmed by serum beta human chorionic gonadotropin (ß HCG) test ≤7 days prior to randomization) or lactating
* History of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
* Acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator
* Grade 3 or higher bleeding event ≤3 months prior to randomization
* Experience of any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event, Grade 4 hypertension, Grade 3 proteinuria, a Grade 3-4 bleeding event, or bowel perforation
* Known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: UGT1A1\*6/\*6, UGT1A1\*28/\*28, or UGT1A1\*6/\*28
* Known allergy to any of the study treatment components, including any components used in the preparation of ramucirumab, or other contraindication to receive the study treatments
* Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis

Answer: C