5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer

NCT ID: NCT00308516

Last Updated: 2021-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2012-02-29

Brief Summary

This phase II trial will investigate the combination of adjuvant 5-fluorouracil, radiation, and bevacizumab in patients with stage II and III rectal cancer, followed by FOLFOX6 and bevacizumab. Fluorouracil (FU) has proven to be an effective and safe regimen in the treatment of stage II and III rectal cancer. Recent evidence has proven fluorouracil/leucovorin (FL) in combination with bevacizumab is superior to FL alone and when combined with irinotecan is superior to (irinotecan plus fluorouracil/leucovorin (IFL) alone. This trial will be one of the first clinical trials to evaluate a combination of targeted therapy, radiation, and chemotherapy in the adjuvant treatment of a common solid tumor.

Detailed Description

All eligible patients will receive combined modality treatment initially. Systemic treatment will begin 4-6 weeks after completion of the Combined Modality portion and will complete 4 cycles of a 4 week regimen. Patients with no evidence of disease following systemic therapy may continue single agent bevacizumab for up to one year. After all treatment is completed, patients will be re-evaluated with imaging to establish a new baseline. Patients will be re-evaluated thereafter for up to a total of 5 years.

Combined Modality Treatment:

• bevacizumab 5mg/kg IV infusion days 1, 15, and 29
• fluorouracil 225mg/m2 IV continuous infusion days 1-42
• radiation 1.8 Gy/day or 28 fractions weeks 1-6

Systemic Treatment:

• 5-fluorouracil 400 mg/m2 bolus
• 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15
• leucovorin 350 mg prior to FU on days 1 and 15
• oxaliplatin 85 mg/m2 days 1 and 15
• bevacizumab 5 mg/kg days 1 and 15

Conditions

Rectal Cancer; Cancer of the Rectum; Colorectal Cancer

Keywords

Rectal Cancer; Cancer of the Rectum; Colorectal Cancer; Bevacizumab

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A - Preoperative

Each patient enrolled in the preoperative cohort received 5-fluorouracil (5-FU) 225 mg/m2 as a continuous infusion (IVCI) on days 1-42 through a portable infusion pump and central venous catheter. Bevacizumab 5 mg/kg was administered intravenously (IV) on days 1 and 15. Additionally these patients received radiation therapy to 50.4 Gy (1.8 Gy/day or 28 fractions) Monday through Friday during weeks 1-6.

At least 8 weeks after surgery, patients in cohort A began 4 months of chemotherapy and bevacizumab. This adjuvant treatment consisted of 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: DRUG

Combined Modality Treatment:

fluorouracil 225mg/m2 IV continuous infusion days 1-42

Systemic Treatment:

5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15

Bevacizumab

Intervention Type: DRUG

Combined Modality Treatment:

bevacizumab 5mg/kg IV infusion days 1, 15, and 29

Systemic Treatment:

bevacizumab 5 mg/kg days 1 and 15

Radiation Therapy

Intervention Type: PROCEDURE

radiation 1.8 Gy/day or 28 fractions weeks 1-6

Oxaliplatin

Intervention Type: DRUG

Systemic Treatment:

oxaliplatin 85 mg/m2 days 1 and 15

Leucovorin

Intervention Type: DRUG

Systemic Treatment:

leucovorin 350 mg prior to FU on days 1 and 15

Cohort B - Combined Modality

All patients enrolled in cohort B received 5-fluorouracil (5-FU) 225 mg/m2 IVCI on days 1-42. Bevacizumab was administered at 5 mg/kg IV on day 1 every 2 weeks. These patients also received radiation to 50.4 Gy (1.8 Gy/day or 28 fractions)Monday through Friday during weeks 1-6.

Six weeks after the completion of adjuvant 5-FU/radiation, patients began treatment with 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: DRUG

Combined Modality Treatment:

fluorouracil 225mg/m2 IV continuous infusion days 1-42

Systemic Treatment:

5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15

Bevacizumab

Intervention Type: DRUG

Combined Modality Treatment:

bevacizumab 5mg/kg IV infusion days 1, 15, and 29

Systemic Treatment:

bevacizumab 5 mg/kg days 1 and 15

Radiation Therapy

Intervention Type: PROCEDURE

radiation 1.8 Gy/day or 28 fractions weeks 1-6

Oxaliplatin

Intervention Type: DRUG

Systemic Treatment:

oxaliplatin 85 mg/m2 days 1 and 15

Leucovorin

Intervention Type: DRUG

Systemic Treatment:

leucovorin 350 mg prior to FU on days 1 and 15

Interventions

5-Fluorouracil

Combined Modality Treatment:

fluorouracil 225mg/m2 IV continuous infusion days 1-42

Systemic Treatment:

5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15

Intervention Type: DRUG

Bevacizumab

Combined Modality Treatment:

bevacizumab 5mg/kg IV infusion days 1, 15, and 29

Systemic Treatment:

bevacizumab 5 mg/kg days 1 and 15

Intervention Type: DRUG

Radiation Therapy

radiation 1.8 Gy/day or 28 fractions weeks 1-6

Intervention Type: PROCEDURE

Oxaliplatin

Systemic Treatment:

oxaliplatin 85 mg/m2 days 1 and 15

Intervention Type: DRUG

Leucovorin

Systemic Treatment:

leucovorin 350 mg prior to FU on days 1 and 15

Intervention Type: DRUG

Other Intervention Names

Fluorouracil; Efudex; 5-FU; Avastin; Eloxatin; Folinic acid

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed Stage I or II rectal cancer
• Patients must be candidates for preoperative or adjuvant chemoradiation.
• Patients enrolling in the adjuvant chemoradiation cohort must have undergone surgical resection of the primary rectal tumor between 28 and 56 days (i.e., 4-8 weeks) prior to study treatment.
• ECOG performance status 0-1
• Adequate bone marrow, liver, and kidney function
• At least 18 years of age
• Able to give written informed consent

Exclusion Criteria

• Treatment with prior chemotherapy or radiation for rectal cancer
• History of myocardial infarction
• Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication or peripheral vascular disease
• History of stroke within 6 months
• History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months
• Symptomatic sensory or peripheral neuropathy
• Prior treatment with anti-angiogenic agents
• Prior malignancy in the past 5 years
• Active infections or serious underlying medical condition
• Major surgery less than 28 days prior
• Women who are pregnant or lactating
• Thrombolytic therapy within 10 days of starting bevacizumab
• PEG tube, G-tube, or external biliary stents
• Proteinuria
• Non healing wound, ulcer or fracture
• History of bleeding diathesis or coagulopathy
• Hemoptysis
• Participation in another experimental trial within 28 days
• Uncontrolled anticoagulant therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David R. Spigel, MD

Role: PRINCIPAL_INVESTIGATOR

SCRI Development Innovations, LLC

Locations

Northeast Alabama Regional Medical Center

Anniston, Alabama, United States

Northeast Arkansas Clinic

Jonesboro, Arkansas, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Integrated Community Oncology Network

Jacksonville, Florida, United States

Watson Clinic Center for Cancer Care and Research

Lakeland, Florida, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Wellstar Cancer Research

Marietta, Georgia, United States

Consultants in Blood Disorders and Cancer

Louisville, Kentucky, United States

Consultants in Medical Oncology and Hematology

Drexel Hill, Pennsylvania, United States

Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

South Texas Oncology and Hematology

San Antonio, Texas, United States

Peninsula Cancer Institute

Newport News, Virginia, United States

Countries

United States

References

Spigel DR, Bendell JC, McCleod M, Shipley DL, Arrowsmith E, Barnes EK, Infante JR, Burris HA 3rd, Greco FA, Hainsworth JD. Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer. Clin Colorectal Cancer. 2012 Mar;11(1):45-52. doi: 10.1016/j.clcc.2011.04.002. Epub 2011 Aug 15.

Reference Type: BACKGROUND

PMID: 21840771 (View on PubMed)

Other Identifiers

AVF3105s

Identifier Type: OTHER

Identifier Source: secondary_id

SCRI GI 65

Identifier Type: -

Identifier Source: org_study_id