Clinical trial NCT00308516: 5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectal Cancer
Cancer of the Rectum
Colorectal Cancer
Keywords: Rectal Cancer
Cancer of the Rectum
Colorectal Cancer
Bevacizumab
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2006-03-29
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
timeFrame: 24 months
Secondary outcomes:
measure: Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
timeFrame: 24 months
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: Jonesboro
country: United States
facility: Northeast Arkansas Clinic
state: Arkansas
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic Center for Cancer Care and Research
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Marietta
country: United States
facility: Wellstar Cancer Research
state: Georgia
city: Louisville
country: United States
facility: Consultants in Blood Disorders and Cancer
state: Kentucky
city: Drexel Hill
country: United States
facility: Consultants in Medical Oncology and Hematology
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology
state: Texas
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: David R. Spigel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.