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Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil and Leucovorin vs Oxaliplatin, 5-Fluorouracil, Leucovorin and Bevacizumab for Patients With Stage II or III Rectal Ca

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Trial Conditions
  • Colorectal Cancer
  • Adenocarcinoma of the Rectum
  • Stage II Rectal Cancer
  • Stage III Rectal Cancer
What is the purpose of this trial?

Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether oxaliplatin, leucovorin, and fluorouracil is more effective with or without bevacizumab in treating rectal cancer. This randomized phase III trial is studying combination chemotherapy to see how well it works with or without bevacizumab in treating patients who have had surgery for stage II or stage III rectal cancer.

Date & Status


Who can Participate?


18 and older



Inclusion Criteria:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 3 months
after study treatment

- No other previous or concurrent malignancy except nonmelanoma skin cancer, breast
cancer in situ, carcinoma in situ of the cervix, or previously treated nonpelvic
cancer that has been disease-free for > 5 years

- Patients with a history of breast cancer (without evidence of disease) who remain on
hormonal therapy for > 5 years are eligible

- No active bleeding not related to the primary rectal tumor within the past 6 months

- No active inflammatory bowel disease or other serious medical illness which might
limit the ability of the patient to receive protocol therapy

- No active gastroduodenal ulcer determined by endoscopy

- No serious or nonhealing wound, skin ulcer, or bone fracture

- No clinically significant peripheral sensory or motor neuropathy >= grade 2

- No nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would
preclude study treatment including, but not limited to, any of the following:

- New York Heart Association class III or IV congestive heart failure

- Concurrent symptomatic arrhythmia

- No transient ischemic attack or cerebrovascular accident

- No arterial thromboembolic event, unstable angina, or myocardial infarction within
the past 12 months

- No significant peripheral vascular disease

- No psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude study requirements

- Patients with a history of hypertension must have blood pressure < 150/90 mm Hg AND
be on a stable regimen of antihypertensive therapy

- No significant traumatic injury within the past 28 days

- No known allergy to platinum compounds

- No other prior chemotherapy or pelvic radiotherapy except as neoadjuvant treatment
for current diagnosis of rectal cancer

- No prior invasive procedure, including either of the following:

- Major surgical procedure or open biopsy within the past 28 days

- Core biopsy or other minor procedure, except placement of a vascular access
device, within the past 7 days

- Concurrent participation on protocol NSABP-R-04 allowed

- Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following
clinical (e.g., before neoadjuvant therapy) or pathologic staging criteria:

- T3, N+, M0

- T3, N0, M0

- T4, N0, M0

- Any T, N1-2, M0

- T4, N0-2, M0 disease must meet 1 of the following criteria:

- Clinically fixed tumor on rectal examination with tumor adherent to the pelvic
sidewall or sacrum

- Hydronephrosis on CT scan or IVP

- Ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy

- Invasion into prostate

- Vaginal or uterine involvement

- Must have undergone complete tumor resection >= 28 days ago and able to begin
treatment by day 56

- No evidence of metastatic disease on the surgical/intraoperative examination

- Must have undergone concurrent neoadjuvant chemoradiotherapy*

- Must have undergone prior radiotherapy at 40-55.8 Gy** AND received 1 of the
following chemotherapy regimens:

- Continuous infusion of fluorouracil with or without oxaliplatin; fluorouracil
and leucovorin calcium

- Capecitabine with or without oxaliplatin; capecitabine with or without
oxaliplatin OR a continuous infusion of fluorouracil with or without oxaliplatin
received on protocol NSABP-R-04

- NOTE: *Neoadjuvant chemoradiotherapy received on protocol NSABP-R-04 allowed provided
it met these criteria

- NOTE: **Intensity-modulated radiotherapy allowed

- No evidence of metastatic disease confirmed by CT scan, MRI, or ultrasound of the
liver or chest CT scan or chest x-ray within the past 6 months

- No evidence of tumor outside of the pelvis, including liver metastases, peritoneal
seeding, or metastatic inguinal lymphadenopathy

- ECOG performance status 0-1

- Platelet count >= 100,000/mm^3

- Absolute granulocyte count >= 1,500/mm^3

- Bilirubin normal (unless chronic grade 1 bilirubin elevation due to Gilbert's disease
or similar syndrome due to slow conjugation of bilirubin)

- Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN) and AST < 1.5 times

- Hepatitis B and C negative (for patients with AP > normal) unless previously

- Serum creatinine =< 1.5 times ULN

- Urine protein:creatinine (UPC) ratio < 1.0 OR urine protein < 1 g on 24-hour urine

- INR =< 1.5

- INR > 1.5 allowed provided patient is on full-dose anticoagulants AND meets all of
the following criteria:

- In-range INR (i.e., between 2 and 3) on a stable dose of warfarin or low
molecular weight heparin

- No active bleeding or pathological condition that is associated with a high risk
of bleeding

- No concurrent major surgery

Gender: Both
Steward Physician(s)
  • Al Benson
  • Neal J. Meropol, MD
  • Nicholas J. Petrelli, MD
  • Frank Sinicrope, MD
  • J. D. Brierley, MD
  • St. Elizabeth's Medical Center - Terminated
Trial Interventions
  • oxaliplatin
  • fluorouracil
  • leucovorin calcium
  • bevacizumab
  • laboratory biomarker analysis
Physician Researcher

Investigator Name:

  • Al Benson
  • Neal J. Meropol, MD
  • Nicholas J. Petrelli, MD
  • Frank Sinicrope, MD
  • J. D. Brierley, MD

Other Information

Sponsor: National Cancer Institute (NCI)
Phase: Phase 3
Trial ID: NCT00303628
Volunteers:  Not Accepting Healthy Volunteers

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