5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer
Condition: Rectal Cancer; Cancer of the Rectum; Colorectal Cancer
MeSH terms: Colorectal Neoplasms; Rectal Neoplasms
Intervention: 5-Fluorouracil; Bevacizumab; Radiation Therapy; Oxaliplatin; Leucovorin
Intervention description: 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; Combined Modality Treatment:
bevacizumab 5mg/kg IV infusion days 1, 15, and 29
Systemic Treatment:
bevacizumab 5 mg/kg days 1 and 15; radiation 1.8 Gy/day or 28 fractions weeks 1-6; Systemic Treatment:
oxaliplatin 85 mg/m2 days 1 and 15; Systemic Treatment:
leucovorin 350 mg prior to FU on days 1 and 15
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rectal Cancer; Cancer of the Rectum; Colorectal Cancer; Bevacizumab

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.
    

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