Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Clinical Trial Comparing Preoperative Radiation Therapy And Capecitabine With or Without Oxaliplatin With Preoperative Radiation Therapy And Continuous Intravenous Infusion Of 5-Fluorouracil With or Without Oxaliplatin In The Treatment Of Patients With Operable Carcinoma Of The Rectum
Brief Summary: RATIONALE: Drugs used in chemotherapy, such as capecitabine, fluorouracil, and oxaliplatin work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells.

PURPOSE: This randomized phase III trial is studying radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin and comparing them to see how well they work when given before surgery in treating patients with resectable rectal cancer. It is not yet known whether radiation therapy and either capecitabine or fluorouracil is more effective with or without oxaliplatin in treating rectal cancer.


Options:
A: Inclusion Criteria

1. Signed written informed consent obtained prior to any study specific screening procedures.
2. Patient willing and able to comply with the protocol.
3. Age ≥ 18 years-of-age.
4. Histologically confirmed colon carcinoma, American Joint Cancer Committee/Union Internationale Contre le Cancer (AJCC/UICC) Stage II or Stage III defined as a tumor location ≥ 15 cm from the anal verge by endoscopy or above the peritoneal reflection at surgery. The patient was not to be a candidate for (neo) adjuvant radiotherapy. Note: Stage II patients were to be considered as high-risk patients fulfilling one of the following criteria:

   * T4 tumours,
   * Patients presenting with bowel obstruction or perforation,
   * Histological signs of vascular invasion (i.e. blood and lymphatic vessels) or perineural invasion,
   * Patients aged less than 50 years,
   * Patients with sub-optimal surgery (less than 12 nodes analyzed).
5. Curative surgery not less than 4 and not more than 8 weeks prior to randomization.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Life expectancy of ≥ 5 years.

Exclusion Criteria

1. Macroscopic or microscopic evidence of remaining tumour. Patients should never have had any evidence of metastatic disease (including presence of tumour cells in the ascites). The isolated finding of cytokeratin positive cells in bone marrow is not considered evidence of metastatic disease for purposes of this study.
2. Carcinoembryonic antigen \> 1.5 x upper limit of normal (ULN) after surgery (during screening period).
3. For patients with colostomy, unwilling to delay revision until at least 28 days after treatment completion.
4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, not fully healed wounds, or anticipation of the need for major surgical procedure during the course of the study. Any central venous access device (CVAD) for chemotherapy administration must be inserted at least 2 days prior to treatment start.
5. Previous anti-angiogenic treatment for any malignancy; cytotoxic chemotherapy, radiotherapy or immunotherapy for colon cancer.
6. Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
7. Females with a positive or no pregnancy test (within 7 days before treatment start) unless childbearing potential can be otherwise excluded (postmenopausal i.e. amenorrheic for at least 2 years, hysterectomy or oophorectomy).
8. Lactating women.
9. Fertile women (\< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
10. History or evidence upon physical examination of central nervous disease (CNS) disease (eg, primary brain tumour, seizure not controlled with standard medical therapy, any brain metastases).
11. History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake.
12. Clinically significant (ie, active) cardiovascular disease. This includes, but is not limited to, the following examples: cerebrovascular accidents (≤ 6 months prior to randomization), myocardial infarction (≤ 1 year prior to randomization), uncontrolled hypertension (\>150/100 mmHg) while receiving chronic medication, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, clinically significant electrocardiogram (ECG) findings (e.g. QTc ≥ 440 msecs \[male\] 460 msecs \[female\] or ≥ 2º atrioventricular block, etc.).

    Patients who suffer from serious cardiac arrhythmia requiring medication can enter the study only if they are considered to be in a stable condition regarding both the arrhythmia and their medication. Patients with pacemakers are allowed to enter the study only if they are considered as being in a stable condition. In case of doubt, the investigator should obtain a consultation with a local cardiologist.
13. Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication.
14. Interstitial pneumonia or extensive symptomatic fibrosis of the lungs.
15. Known peripheral neuropathy ≥ Common terminology criteria for adverse events (CTCAE) version 3.0 Grade 1. Absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible.
16. Organ allografts requiring immunosuppressive therapy.
17. Serious, non-healing wound, ulcer, or bone fracture.
18. Evidence of bleeding diathesis or coagulopathy.
19. Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes.
20. Chronic, daily treatment with high-dose aspirin (\> 325 mg/day) or clopidogrel (\> 75 mg/day).
21. Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
22. Serious intercurrent infections (uncontrolled or requiring treatment).
23. Known dihydropyrimidine dehydrogenase deficiency.
24. Current or recent (within the 28 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
25. Patients with known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies or to any excipients of bevacizumab formulation, platinum compounds or to any other components of the study drugs.
26. History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications.
27. Presence of proteinuria at baseline as defined by:

    - Patients with \> 1 g of protein/24 hour by a 24-hour urine collection.
28. Any laboratory values at baseline are as follows:

Haematology:

* Absolute neutrophil count (ANC) \< 1.5 x 109/L
* Platelet count \< 100 x 10\^9/L
* Haemoglobin \< 9 g/dL (may be transfused to maintain or exceed this level)
* International normalized ratio (INR) \> 1.5
* Activated partial prothrombin time (APTT) ≥ 1.5 x ULN

Biochemistry:

* Total bilirubin \> 1.5 x ULN
* aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) \> 2.5 x ULN
* Alkaline phosphatase (ALP) \> 2.5 x ULN
* Serum creatinine \> 1.5 x ULN or creatinine clearance ≤ 50 mL/min (e.g. Cockcroft-Gault formula).
B: DISEASE CHARACTERISTICS:

* Histologically confirmed resectable adenocarcinoma of the rectum

  * Any grade
  * Tumor macroscopically within 15 cm of anal margin on rigid rectoscopy
  * Tumor tethered or partially fixed on digital rectal exam and/or T3-4 on rectal ultrasound
* No acute or subacute bowel obstruction without colostomy diversion
* No chronic inflammatory disease of the ileum and/or colon
* No primary adenocarcinoma of the anal canal
* No distant metastasis

PATIENT CHARACTERISTICS:

Age:

* 80 and under

Performance status:

* WHO 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Granulocyte count greater than 2,000/mm\^3
* Platelet count greater than 130,000/mm\^3

Hepatic:

* Not specified

Renal:

* Creatinine less than 1.36 mg/dL

Cardiovascular:

* No angina pectoris

Other:

* No other prior malignancy except basal cell skin cancer or carcinoma in situ of the uterine cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior biologic therapy for adenocarcinoma of the rectum

Chemotherapy

* No prior chemotherapy for adenocarcinoma of the rectum

Endocrine therapy

* No prior endocrine therapy for adenocarcinoma of the rectum

Radiotherapy

* No prior radiotherapy for adenocarcinoma of the rectum

Surgery

* No prior surgery for adenocarcinoma of the rectum
C: Inclusion Criteria:

* Patients must consent to participate in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines.
* Patients must be \> 18 years of age.
* Patients must have a life expectancy of 5 years, excluding their diagnosis of cancer (as determined by the investigator), and must have an Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0 or 1.
* Patients must have a diagnosis of adenocarcinoma of the rectum obtained by a biopsy technique which leaves the major portion of the tumor intact.
* The interval between the initial diagnosis of rectal adenocarcinoma and randomization must be no more than 42 days.
* Prior to randomization, the investigator must specify the intent for sphincter saving or non-sphincter saving surgery.
* The tumor must be either palpable by digital rectal exam or be accessible via a proctoscope or sigmoidoscope.
* Distal border of the tumor must be located \< 12 cm from the anal verge.
* The tumor must be considered by the surgeon to be amenable to curative resection. (Note that curative resection can include pelvic exenteration.)
* The tumor must be clinically Stage II (T3-4 N0 with N0 being defined as all imaged lymph nodes are \< 1.0 cm) or Stage III (T1-4 N1-2 with the definition of a clinically positive node being any node \> 1.0 cm). Stage of the primary tumor may be determined by ultrasound or Magnetic Resonance Imaging (MRI). Computed Tomography (CT) scan is acceptable provided there is evidence of T4 and/or N1-2 disease.
* At the time of randomization, all patients must have had the following within the previous 42 days: history and physical examination; if technically feasible, a complete colonoscopic examination; if not feasible, a proctoscopic or sigmoidoscopic exam; clinical staging of the tumor; CT or MRI of the abdomen and pelvis (combined PET/CT may be substituted), and a chest x-ray (PA and lateral) or CT scan of the chest to exclude patients with metastatic disease.
* At the time of randomization: Absolute neutrophil count (ANC) must be \> 1,200/mm3; Platelet count must be \> 100,000/mm3; There must be evidence of adequate hepatic function as follows: total bilirubin must be \< 1.5 x the upper limit of normal (ULN) for the lab; and alkaline phosphatase must be \< 2.5 x Upper Limit of Normal (ULN) for the lab; and the Aspartate Amino Transferase (AST) must be \< 2.5 x ULN for the lab; and If AST is \> ULN, serologic testing for Hepatitis B and C must be performed and results must be negative; Calculated creatinine clearance must be \> 50 mL/min.
* Patients with prior malignancies, including invasive colon cancer, are eligible if they have been disease-free for \> 5 years and are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years prior to randomization.

Exclusion Criteria:

* Findings of metastatic disease.
* On imaging, clear indication of involvement of the pelvic side wall(s).
* Rectal cancers other than adenocarcinoma, i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, cloacogenic carcinoma, etc.
* History of invasive rectal malignancy, regardless of disease-free interval.
* Pregnancy or lactation at the time of proposed randomization. Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods.
* Any therapy for this cancer prior to randomization.
* Synchronous colon cancer.
* History of viral hepatitis or other chronic liver disease.
* Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from receiving any chemotherapy treatment option or would prevent required follow-up. Specifically excluded are patients with active ischemic heart disease (class III\* or class IV\*\* myocardial disease as described by the New York Heart Association), a recent history (within 6 months) of myocardial infarction, or symptomatic arrhythmia at the time of randomization. \*Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Such patients are comfortable at rest. Less than ordinary physical activity that causes fatigue, palpitation, dyspnea, or anginal pain. \*\*Class IV: Patients with cardiac disease resulting in inability to perform any physical activity without discomfort. Symptoms of cardiac insufficiency or anginal syndrome may be present even at rest.
* Patients who, in the opinion of the investigator, have uncontrolled hypertension.
* Active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic).
* Prior pelvic radiation therapy for any reason.
* Known hypersensitivity to 5-fluorouracil, capecitabine, or oxaliplatin.
* Clinically significant peripheral neuropathy at the time of randomization (defined in the NCI Common Terminology Criteria for Adverse Events Version 3.0 \[CTCAE v3.0\] as grade 2 or greater neurosensory or neuromotor toxicity).
* Existing uncontrolled coagulopathy.
* Inability to take oral medications.
* Participation in any investigational drug study within 4 weeks prior to randomization.
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
D: Participants who met the following main selection criteria were included in the study.

Inclusion Criteria:

* Histologically or cytologically proven adenocarcinoma of the colon or rectum
* Metastatic disease that is not amenable to potentially curative treatment
* One and only one prior line of treatment for metastatic disease. This prior line should be an oxaliplatin based chemotherapy (participants who relapse within 6 months of completion of oxaliplatin based adjuvant chemotherapy are eligible)
* Prior treatment with bevacizumab is permitted.

Exclusion Criteria:

* Prior therapy with irinotecan
* Eastern Cooperative Oncology Group performance status \>2

The above information is not intended to contain all considerations relevant to participation in a clinical trial.

Answer: C