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

Colorectal Cancer Clinical Trial

Official title:

A Phase II Study of 5-Fluorouracil, Bevacizumab (Avastin), and Radiation in the Preoperative or Adjuvant Treatment of Patients With Stage II / III Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00308516
• Other study ID #: SCRI GI 65
• Secondary ID: AVF3105s
• Status: Completed
• Phase: Phase 2
• Start date: March 2006
• Est. completion date: February 2012

Study information

• Verified date: November 2021
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: February 2012
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer of the Rectum
• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• 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
• Bevacizumab
Combined Modality Treatment: bevacizumab 5mg/kg IV infusion days 1, 15, and 29 Systemic Treatment: bevacizumab 5 mg/kg days 1 and 15

Procedure:
• Radiation Therapy
radiation 1.8 Gy/day or 28 fractions weeks 1-6

Drug:
• Oxaliplatin
Systemic Treatment: oxaliplatin 85 mg/m2 days 1 and 15
• Leucovorin
Systemic Treatment: leucovorin 350 mg prior to FU on days 1 and 15

Locations

Country	Name	City	State
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	Consultants in Medical Oncology and Hematology	Drexel Hill	Pennsylvania
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	Northeast Arkansas Clinic	Jonesboro	Arkansas
United States	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	Wellstar Cancer Research	Marietta	Georgia
United States	Tennessee Oncology	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	South Texas Oncology and Hematology	San Antonio	Texas
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment	The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment	24 months
Secondary	Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death	Overall Survival (OS) is defined ad the Length of time, in months, that patients were alive from their first date of protocol treatment until death.	24 months