Clinical trial NCT00308516
Conditions: Rectal Cancer Cancer of the Rectum Colorectal Cancer
Keywords: Rectal Cancer Cancer of the Rectum Colorectal Cancer Bevacizumab
Sponsor: SCRI Development Innovations, LLC
Start date: 2006-03-01; Completion date: 2012-02-01
Enrollment: 66 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: 5-Fluorouracil intervention 2: Bevacizumab intervention 3: Radiation Therapy intervention 4: Oxaliplatin intervention 5: Leucovorin
Intervention descriptions: intervention 1: 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 2: Combined Modality Treatment:

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

Systemic Treatment:

bevacizumab 5 mg/kg days 1 and 15 intervention 3: radiation 1.8 Gy/day or 28 fractions weeks 1-6 intervention 4: Systemic Treatment:

oxaliplatin 85 mg/m2 days 1 and 15 intervention 5: Systemic Treatment:

leucovorin 350 mg prior to FU on days 1 and 15

Protocol documents: