Trial record 1 of 1 for:    ECOG E5202
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Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00217737
First received: September 20, 2005
Last updated: March 18, 2014
Last verified: February 2014
  Purpose

This randomized phase III trial is studying oxaliplatin, leucovorin, fluorouracil, and bevacizumab to see how well they work compared to oxaliplatin, leucovorin, and fluorouracil or observation only in treating patients who have undergone surgery for stage II colon cancer. 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 combination chemotherapy together with bevacizumab after surgery may kill any remaining tumor cells or prevent the cancer from coming back. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving combination chemotherapy together with bevacizumab is more effective than combination chemotherapy alone or observation only in treating colon cancer.


Condition Intervention Phase
Adenocarcinoma of the Colon
Stage II Colon Cancer
Other: clinical observation
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Biological: bevacizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Study Comparing 5-FU, Leucovorin and Oxaliplatin Versus 5-FU, Leucovorin, Oxaliplatin and Bevacizumab in Patients With Stage II Colon Cancer at High Risk for Recurrence to Determine Prospectively the Prognostic Value of Molecular Markers

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    A stratified log-rank test, with stratification on stage (IIA versus IIB) and MSI status (MSS versus MSI-L) will be used.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Rates of all toxicities and in particular those events that may be elevated due to the addition of bevacizumab (perforation, thrombosis, delays in wound healing) assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    We will tabulate and report adverse events by treatment arm and note those events that differ statistically between arms. No formal type I error adjustment will be done for the toxicity analyses.

  • Impact of tumor biologic characteristics and their relationship to overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Analysis of tumor biological characteristics and their relationship to overall survival will be conducted between high and low risk populations.


Enrollment: 2389
Study Start Date: August 2005
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (chemotherapy)
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV bolus followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Experimental: Arm II (chemotherapy and antibody therapy)
Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Arm III (observation)
Patients undergo observation only.
Other: clinical observation
No intervention
Other Name: observation

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare the 3-year disease-free survival of patients with resected stage II colon cancer at high risk for recurrence treated with oxaliplatin, leucovorin calcium, and fluorouracil with vs without bevacizumab.

SECONDARY OBJECTIVES:

I. Compare the overall survival of patients treated with these regimens. II. Compare the toxicity profiles of these regimens in these patients. III. Correlate tumor biologic characteristics with survival of patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to disease stage (IIA vs IIB) and microsatellite instability (MSI) status (microsatellite stable [MSS] vs low levels of microsatellite instability [MSI-L]). Patients with disease that is at high risk for MSI and loss of heterozygosity (LOH) at chromosome 18q are randomized to 1 of 2 treatment arms (arms I and II). Patients with disease that is at low risk for MSI and 18q LOH are assigned to arm III.

ARM I: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV bolus followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.

ARM III: Patients undergo observation only.

Patients are followed every 3 months for 1-2 years, every 6 months for 3 years, and then annually for up to 10 years from study entry.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the colon

    • Stage II disease (pT3, pT4a-b, N0, M0)

      • At least 8 lymph nodes must have been evaluated
  • Meets 1 of the following criteria:

    • High risk for microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 18q

      • Microsatellite stable (MSS) with 18q LOH
      • MSI-low grade (MSI-L) with 18q LOH
    • Low risk for MSI and 18q LOH

      • MSS with retention of 18q alleles
      • MSI-L with retention of 18q alleles
      • MSI-high grade (MSI-H) with retention of 18q alleles
      • MSI-H without retention of 18q alleles
      • MSI-H with 18q status uninformative
  • Distal extent of tumor must be ≥ 12 cm from the anal verge by endoscopy or surgical examination

    • If tumor is located beyond sigmoid colon and centimeter distance is unavailable, include anatomic region of the colon (e.g., right colon, transverse colon, hepatic flexure, descending colon, or cecum)
  • Has undergone surgical resection of the tumor between the past 28-60 days

    • Must have had a complete resection (R0 resection)
  • No history of isolated, distant, or noncontiguous intra-abdominal metastases
  • Patients with synchronous tumors or appendiceal tumors are ineligible
  • Hereditary non-polyposis colorectal cancer allowed
  • Paraffin-embedded tumor specimen (one with normal mucosa and one from the resection tumor) available
  • Performance status - ECOG 0-2
  • Absolute granulocyte count ≥ 1,500/mm^3*
  • Platelet count ≥ 100,000/mm^3*
  • No significant bleeding unrelated to tumor within the past 6 months*
  • Bilirubin normal (unless due to Gilbert's disease or similar syndrome)*
  • Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN)*
  • AST < 1.5 times ULN*
  • PT INR > 1.5* allowed provided the following criteria are met:

    • Patient is on full-dose anticoagulants
    • INR in range (usually 2-3) on a stable dose of warfarin or low molecular weight heparin
    • No active bleeding or pathological condition associated with a high risk of bleeding unrelated to primary colon tumor
  • No systemic hepatic disease*
  • Creatinine ≤ 1.5 times ULN*
  • Urine protein:creatinine ratio < 1.0*
  • Urine protein < 1 gm on 24-hour urine collection*
  • No systemic renal disease*
  • History of hypertension allowed provided blood pressure < 150/90 mm Hg while on a stable regimen of anti-hypertensive therapy*
  • No New York Heart Association class III or IV cardiac disease*
  • No symptomatic arrhythmia*
  • No history of transient ischemic attack*
  • No history of cerebrovascular accident*
  • No symptomatic peripheral vascular disease*
  • No arterial thromboembolic events within the past 12 months*
  • No unstable angina within the past 12 months*
  • No myocardial infarction within the past 12 months*
  • No other systemic cardiovascular disease*
  • Not pregnant or nursing*
  • Negative pregnancy test*
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment*
  • No active gastroduodenal ulcer by endoscopy*
  • No complete obstruction or perforation of the bowel
  • No history of inflammatory bowel disease
  • No prior or concurrent malignancy except for nonmelanoma skin cancer, carcinoma in situ of the cervix, breast cancer in situ, treated non-pelvic cancer from which the patient has been disease-free for > 5 years, or history of breast cancer (without evidence of disease) and remain on hormonal therapy for > 5 years
  • No other nonmalignant systemic disease that would preclude study compliance*
  • No psychiatric or addictive disorder or other condition that would preclude study participation*
  • No serious or non-healing wound, skin ulcer, or bone fracture*
  • No peripheral neuropathy ≥ grade 2*
  • No significant traumatic injury within the past 4 weeks*
  • No known allergy to platinum compounds
  • No prior radiotherapy for this cancer
  • No prior systemic therapy for this cancer
  • More than 28 days since prior major surgery or open biopsy*
  • More than 7 days since prior core biopsy or other minor procedure except placement of a vascular access device*
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00217737

  Show 866 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: NCT00217737     History of Changes
Other Study ID Numbers: NCI-2009-00562, NCI-2009-00562, ECOG-E5202, CDR0000443410, E5202, E5202, U10CA021115
Study First Received: September 20, 2005
Last Updated: March 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Colonic 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
Colonic Diseases
Intestinal 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 April 20, 2014