Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised Study of Sequential Versus Combination Chemotherapy in Patients With Previously Untreated Advanced Colorectal Carcinoma
Brief Summary: Primary objective:To assess the efficacy, defined as overall survival, of sequential versus combination chemotherapy for advanced colorectal cancer (CRC).

Methodology Open, randomised multicenter phase III study. Randomisation by centre will be centralized. 820 patiënts with histologically proven advanced CRC; not amenable to curative surgery. Measurable or evaluable disease. Age 18 years and above. WHO performance status 0-2.

Test products:

Arm A: First line: capecitabine capecitabine 1250 mg/m2 orally b.i.d. on day 1-14 (q3),until progression or unacceptable toxicity. Second line: irinotecan 350 mg/m2 IV infusion on day 1 (q3),until progression or unacceptable toxicity. Third line: oxaliplatin 130 mg/m2 IV infusion on day 1 and capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (q3). Arm B: First line: irinotecan 250 mg/m2 IV infusion in 30 minutes on day 1 and capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (q3), until progression or unacceptable toxicity. Second line: oxaliplatin 130 mg/m2 IV on day 1 and capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (q3), until progression or unacceptable toxicity.

Patients will be followed by CT-scan every 9 weeks for response while on treatment, or at any other moment when progression is suspected. After cessation of chemotherapy, patients will be followed every 3 months until death. Clinical and laboratory toxicity/symptomatology will be graded according to NCI common criteria.


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: DISEASE CHARACTERISTICS:

* Histologically confirmed colorectal adenocarcinoma

  * Metastatic or unresectable disease
* Progressive disease based on the following criteria:

  * Progression during or after first-line chemotherapy for metastatic disease, including any of the following:

    * Fluoropyrimidine-based monotherapy with bevacizumab
    * Fluoropyrimidine and irinotecan hydrochloride-based doublet with bevacizumab
    * Fluoropyrimidine and oxaliplatin-based doublet with bevacizumab
  * Progression after more than 3 months from the last administration of first-line chemotherapy for metastatic disease with a fluoropyrimidine, irinotecan hydrochloride, and oxaliplatin triplet (FOLFOXIRI) with bevacizumab to which the patient had previously responded
* Measurable disease, as assessed by RECIST criteria
* No prior or concurrent CNS metastasis

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 3 months
* ANC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL
* INR ≤ 1.5 times upper limit of normal (ULN)
* aPTT ≤ 1.5 ULN
* Serum bilirubin ≤ 1.5 times ULN
* AST and ALT ≤ 2.5 times ULN (\< 5 times ULN if liver metastases present)
* Alkaline phosphatase ≤ 2.5 times ULN (\< 5 times ULN if liver metastases present)
* Serum creatinine ≤ 1.5 times ULN
* Proteinuria \< 2+ OR protein ≤ 1g by 24-hour urine
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No bowel obstruction or subobstruction
* No history of inflammatory enteropathy
* No prior extensive intestinal resection (i.e., \> hemicolectomy or extensive small intestine resection with chronic diarrhea)
* No symptomatic peripheral neuropathy \> grade 2
* No active uncontrolled infection
* No active disseminated intravascular coagulation
* No prior or concurrent malignancy, except for curatively treated basal cell and squamous cell carcinoma of the skin, or in situ carcinoma of the cervix
* No clinically significant cardiovascular disease, including any of the following:

  * Cerebrovascular accident within the past 6 months
  * Myocardial infarction within the past 6 months
  * Unstable angina
  * NYHA class II-IV chronic heart failure
  * Uncontrolled arrhythmia
* No uncontrolled hypertension
* No thromboembolic or hemorrhagic events within the past 6 months
* No evidence of bleeding diathesis or coagulopathy
* No serious, non healing wound/ulcer or serious bone fracture
* No significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 6 weeks since prior radiotherapy
* At least 4 weeks since prior surgery
* No prior first-line chemotherapy for metastatic disease without bevacizumab
* No prior cetuximab or other investigational agents
* More than 28 days since prior open biopsy
* More than 28 days since prior and no concurrent major surgical procedure
* No concurrent therapeutic anticoagulation, antiplatelet agents, or NSAID with anti-platelet activity

  * Acetylsalicylic acid ≤ 325 mg/day allowed
C: Inclusion Criteria:

* Histology and staging disease

  * Histologically proven CRC; advanced disease, not amenable to curative surgery;
  * Of Note: In case of a single metastasis, histological or cytological proof of colorectal carcinoma should be obtained prior to randomisation.
  * Measurable or evaluable disease; Serum CEA as the only parameter for disease activity is not allowed.
* General conditions

  * Written informed consent;
  * Age 18 years and above;
  * WHO performance status 0-2;
  * Adequate bone marrow function(WBC \> 3.0 x 109/L, platelets \> 100 x 109/L, Hb \> 6 mmol/L);
  * Adequate hepatic function: total bilirubin \< 1. 5 x upper normal limit, ASAT and ALAT \< 3 x upper normal limits; in case of liver metastases \< 5 x upper normal limits
  * Adequate renal function: creatinin \< 1. 5 x upper normal limits.
* Other - Expected adequacy of follow-up.

Exclusion Criteria:

* General conditions

  * Pregnancy or lactation;
  * Patients (M/F) with reproductive potential not implementing adequate contraceptives measures.
* Prior or current history

  * Prior chemotherapy for advanced disease; prior adjuvant chemotherapy is allowed provided that the last administration was given \> 6 months prior to randomisation.
  * Serious concomitant diseases preventing the safe administration of chemotherapy or likely to interfere with the study assessments;
  * Serious active infections;
  * Inflammatory bowel disease or other diseases associated with chronic diarrhoea;
  * Previous extensive irradiation of the pelvis or abdomen;
  * Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin.
* Concomitant treatments

  * Concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation;
  * Concurrent treatment with any other anti-cancer therapy.
D: Inclusion Criteria:

* Histologically confirmed colorectal cancer
* Locally advanced and/or metastatic colorectal cancer
* Have prior chemotherapy as first line treatment
* No prior irinotecan administration
* Able to take oral medication
* Age 20 to 75
* Performance status 0 or 1 (ECOG)
* WBC 3,000-12,000 / mm\^3
* Platelet ≥100,000 / mm\^3
* AST and ALT ≤ 100 IU/L
* Creatinine ≤ 1.2 mg/dL
* Bilirubin ≤ 1.5 mg/dL

Exclusion Criteria:

* Prior radio therapy for colorectal cancer
* Other malignancies in the past 5 years
* Serious illness or medical condition

Answer: C