Postoperative Chemotherapy With or Without Bevacizumab for Patients With Stage II or III Rectal Cancer

This study has been terminated.
(The study was terminated before reaching its accrual goal due to slow accrual.)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
ClinicalTrials.gov Identifier:
NCT00303628
First received: March 15, 2006
Last updated: July 13, 2016
Last verified: July 2016
  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
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 Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 5-year Overall Survival Rate [ Time Frame: Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization ] [ Designated as safety issue: No ]
    Overall survival (OS) was defined as time from randomization to date of death from any cause. Patients who were still alive were censored at last date of known alive. Kaplan-Meier method was used to estimate the 5-year OS rate.


Secondary Outcome Measures:
  • 5-year Disease-free Survival Rate [ Time Frame: Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization ] [ Designated as safety issue: No ]
    Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer or death, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Kaplan-Meier method was used to estimate 5-year DFS rate.

  • Patterns of Failure [ Time Frame: Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization ] [ Designated as safety issue: No ]
    Failure included recurrence, second primary cancer and death without recurrence.

  • Proportion of Patients Who Completed 12 Cycles of Treatment [ Time Frame: assessed at the end of treatment ] [ Designated as safety issue: No ]
    In the study, treatment was repeated every 2 weeks for a total of 12 cycles on both arms. The total number of cycles of treatment patient received until going off treatment due to any reason was recorded. It was a measure of the tolerance of the therapy.


Other Outcome Measures:
  • Change in Rectal Function Between Baseline and 12 Months [ Time Frame: assessed at baseline and 12 months after randomization ] [ Designated as safety issue: No ]
    Change in rectal function between baseline and 12 months was measuring the long-term rectal function among the patients. Rectal function was measured using the Bowel Function Questionnaire at baseline and 12 months after randomization. The total score of the questionnaire was calculated as the number of problems with bowel function (score range 0-11). Change in rectal function between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated improved rectal function. This change in score was calculated for each individual patient who had the data.

  • Change in Oxaliplatin-related Neurotoxicity Between Baseline and 12 Months [ Time Frame: assessed at baseline and 12 months after randomization ] [ Designated as safety issue: No ]
    Change in oxaliplatin-related neurotoxicity between baseline and 12 months was measuring the long-term symptom of oxaliplatin-related neurotoxicity among the patients. Oxaliplatin-related neurotoxicity was measured using the FACT/GOG-Ntx subscale at baseline and 12 months after randomization. The range of the total score of the scale was between 0 and 44, and lower values indicate higher neurotoxicity. Change in oxaliplatin-related neurotoxicity between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated worsened symptom. This change in score was calculated for each individual patient who had the data.


Enrollment: 355
Study Start Date: February 2006
Estimated Study Completion Date: April 2019
Primary Completion Date: April 2015 (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
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 Computed Tomography (CT) scan or Intravenous Pyelogram (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
  • Must have undergone concurrent neoadjuvant chemoradiotherapy*

    • NOTE: *Neoadjuvant chemoradiotherapy received on protocol NSABP-R-04 allowed provided it met these criteria
  • 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: **Intensity-modulated radiotherapy allowed
  • 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 aspartate aminotransferase (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
  • International Normalized Ratio (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
  • 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
  • Patients with a history of hypertension must have blood pressure < 150/90 mm Hg AND be on a stable regimen of antihypertensive therapy
  • No other prior chemotherapy or pelvic radiotherapy except as neoadjuvant treatment for current diagnosis of rectal cancer
  • Concurrent participation on protocol NSABP-R-04 allowed

Exclusion Criteria:

  • Pregnant or nursing
  • Evidence of metastatic disease on the surgical/intraoperative examination
  • Evidence of metastatic disease confirmed by CT scan, Magnetic resonance imaging (MRI), or ultrasound of the liver or chest CT scan or chest x-ray within the past 6 months
  • Evidence of tumor outside of the pelvis, including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
  • Concurrent major surgery
  • Active bleeding not related to the primary rectal tumor within the past 6 months
  • Active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy
  • Active gastroduodenal ulcer determined by endoscopy
  • Serious or nonhealing wound, skin ulcer, or bone fracture
  • Clinically significant peripheral sensory or motor neuropathy >= grade 2
  • 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
  • Transient ischemic attack or cerebrovascular accident
  • Arterial thromboembolic event, unstable angina, or myocardial infarction within the past 12 months
  • Significant peripheral vascular disease
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude study requirements
  • Significant traumatic injury within the past 28 days
  • Known allergy to platinum compounds
  • 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
  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
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Al Benson Eastern Cooperative Oncology Group
  More Information

Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT00303628     History of Changes
Other Study ID Numbers: E5204  NCI-2009-00563  CDR0000467561  E5204  U10CA021115 
Study First Received: March 15, 2006
Results First Received: January 28, 2016
Last Updated: July 13, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Keywords provided by Eastern Cooperative Oncology Group:
Rectal cancer
Bevacizumab

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
Bevacizumab
Oxaliplatin
Fluorouracil
Leucovorin
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Calcium, Dietary
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 29, 2016