Postoperative Chemotherapy With or Without Bevacizumab for Patients With Stage II or III Rectal Cancer
Condition: Adenocarcinoma of the Rectum; Stage II Rectal Cancer; Stage III Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: oxaliplatin; fluorouracil; leucovorin calcium; bevacizumab
Intervention description: Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Bevacizumab; Antineoplastic Agents, Immunological; Fluorouracil; Oxaliplatin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 355.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rectal cancer; Bevacizumab

Summary:

      Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop
      the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug
      (combination chemotherapy) together with bevacizumab after surgery may kill any tumor cells
      that remain after surgery. It is not yet known whether oxaliplatin, leucovorin, and
      fluorouracil is more effective with or without bevacizumab in treating rectal cancer. This
      randomized phase III trial is studying combination chemotherapy to see how well it works with
      or without bevacizumab in treating patients who have had surgery for stage II or stage III
      rectal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following
             clinical (e.g., before neoadjuvant therapy) or pathologic staging criteria:

               -  T3, N+, M0

               -  T3, N0, M0

               -  T4, N0, M0

               -  Any T, N1-2, M0

          -  T4, N0-2, M0 disease must meet 1 of the following criteria:

               -  Clinically fixed tumor on rectal examination with tumor adherent to the pelvic
                  sidewall or sacrum

               -  Hydronephrosis on Computed Tomography (CT) scan or Intravenous Pyelogram (IVP)

               -  Ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy

               -  Invasion into prostate

               -  Vaginal or uterine involvement

          -  Must have undergone complete tumor resection >= 28 days ago and able to begin
             treatment by day 56

          -  Must have undergone concurrent neoadjuvant chemoradiotherapy*

               -  NOTE: *Neoadjuvant chemoradiotherapy received on protocol NSABP-R-04 allowed
                  provided it met these criteria

          -  Must have undergone prior radiotherapy at 40-55.8 Gy** AND received 1 of the following
             chemotherapy regimens:

               -  Continuous infusion of fluorouracil with or without oxaliplatin; fluorouracil and
                  leucovorin calcium

               -  Capecitabine with or without oxaliplatin; capecitabine with or without
                  oxaliplatin OR a continuous infusion of fluorouracil with or without oxaliplatin
                  received on protocol NSABP-R-04

               -  NOTE: **Intensity-modulated radiotherapy allowed

          -  ECOG performance status 0-1

          -  Platelet count >= 100,000/mm^3

          -  Absolute granulocyte count >= 1,500/mm^3

          -  Bilirubin normal (unless chronic grade 1 bilirubin elevation due to Gilbert's disease
             or similar syndrome due to slow conjugation of bilirubin)

          -  Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN) and aspartate
             aminotransferase (AST) < 1.5 times ULN

          -  Hepatitis B and C negative (for patients with AP > normal) unless previously
             vaccinated

          -  Serum creatinine =< 1.5 times ULN

          -  Urine protein:creatinine (UPC) ratio < 1.0 OR urine protein < 1 g on 24-hour urine
             collection

          -  International Normalized Ratio (INR) =< 1.5

          -  INR > 1.5 allowed provided patient is on full-dose anticoagulants AND meets all of the
             following criteria:

               -  In-range INR (i.e., between 2 and 3) on a stable dose of warfarin or low
                  molecular weight heparin

               -  No active bleeding or pathological condition that is associated with a high risk
                  of bleeding

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for at least 3 months
             after study treatment

          -  No other previous or concurrent malignancy except nonmelanoma skin cancer, breast
             cancer in situ, carcinoma in situ of the cervix, or previously treated nonpelvic
             cancer that has been disease-free for > 5 years

          -  Patients with a history of breast cancer (without evidence of disease) who remain on
             hormonal therapy for > 5 years are eligible

          -  Patients with a history of hypertension must have blood pressure < 150/90 mm Hg AND be
             on a stable regimen of antihypertensive therapy

          -  No other prior chemotherapy or pelvic radiotherapy except as neoadjuvant treatment for
             current diagnosis of rectal cancer

          -  Concurrent participation on protocol NSABP-R-04 allowed

        Exclusion Criteria:

          -  Pregnant or nursing

          -  Evidence of metastatic disease on the surgical/intraoperative examination

          -  Evidence of metastatic disease confirmed by CT scan, Magnetic resonance imaging (MRI),
             or ultrasound of the liver or chest CT scan or chest x-ray within the past 6 months

          -  Evidence of tumor outside of the pelvis, including liver metastases, peritoneal
             seeding, or metastatic inguinal lymphadenopathy

          -  Concurrent major surgery

          -  Active bleeding not related to the primary rectal tumor within the past 6 months

          -  Active inflammatory bowel disease or other serious medical illness which might limit
             the ability of the patient to receive protocol therapy

          -  Active gastroduodenal ulcer determined by endoscopy

          -  Serious or nonhealing wound, skin ulcer, or bone fracture

          -  Clinically significant peripheral sensory or motor neuropathy >= grade 2

          -  Nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would
             preclude study treatment including, but not limited to, any of the following:

               -  New York Heart Association class III or IV congestive heart failure

               -  Concurrent symptomatic arrhythmia

          -  Transient ischemic attack or cerebrovascular accident

          -  Arterial thromboembolic event, unstable angina, or myocardial infarction within the
             past 12 months

          -  Significant peripheral vascular disease

          -  Psychiatric or addictive disorders or other conditions that, in the opinion of the
             investigator, would preclude study requirements

          -  Significant traumatic injury within the past 28 days

          -  Known allergy to platinum compounds

          -  Prior invasive procedure, including either of the following:

               -  Major surgical procedure or open biopsy within the past 28 days

               -  Core biopsy or other minor procedure, except placement of a vascular access
                  device, within the past 7 days