Combination Chemotherapy With or Without Bevacizumab in Treating Patients Who Have Had Surgery for Stage II or Stage III Rectal Cancer (Groups I and II Closed to Accrual as of 4/29/2009)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00303628
First received: March 15, 2006
Last updated: May 20, 2014
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Rectum
Stage II Rectal Cancer
Stage III Rectal Cancer
Drug: oxaliplatin
Drug: fluorouracil
Drug: leucovorin calcium
Drug: bevacizumab
Procedure: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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 Cancer Receiving Pre-operative Chemoradiation

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Treatment arms compared by stratified log-rank test.


Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Enrollment: 2100
Study Start Date: February 2006
Study Completion Date: February 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Procedure: laboratory biomarker analysis
Correlative study
Experimental: Arm II
Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Procedure: laboratory biomarker analysis
Correlative study

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ULN
  • Hepatitis B and C negative (for patients with AP > normal) unless previously vaccinated
  • Serum creatinine =< 1.5 times ULN
  • Urine protein:creatinine (UPC) ratio < 1.0 OR urine protein < 1 g on 24-hour urine collection
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303628

  Show 617 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Al Benson Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00303628     History of Changes
Other Study ID Numbers: NCI-2009-00563, NCI-2009-00563, E5204, CDR0000467561, E5204, E5204, U10CA021115
Study First Received: March 15, 2006
Last Updated: May 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Antibodies, Monoclonal
Fluorouracil
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014