Bevacizumab, Radiation Therapy, and Combination Chemotherapy in Treating Patients Who Are Undergoing Surgery for Locally Advanced Nonmetastatic Rectal Cancer
Condition: Rectal Adenocarcinoma; Stage II Rectal Cancer AJCC v7; Stage III Rectal Cancer AJCC v7
MeSH terms: Rectal Neoplasms
Intervention: Bevacizumab; Capecitabine; Fluorouracil; Leucovorin Calcium; Oxaliplatin; Radiation Therapy; Therapeutic Conventional Surgery
Intervention description: Given IV; Given PO; Given IV; Given IV; Given IV; Undergo radiotherapy; Undergo surgical resection
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Bevacizumab; Antineoplastic Agents, Immunological; Capecitabine; Fluorouracil; Oxaliplatin; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving bevacizumab, radiation therapy, and combination
      chemotherapy works in treating patients who are undergoing surgery for locally advanced
      nonmetastatic rectal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor
      growth in different ways. Some find tumor cells and kill them or carry tumor-killing
      substances to them. Others interfere with the ability of tumor cells to grow and spread.
      Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.
      Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as capecitabine,
      may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as
      capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving
      bevacizumab together with radiation therapy and combination chemotherapy before surgery may
      make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
      Giving bevacizumab together with combination chemotherapy after surgery may kill any tumor
      cells that remain after surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed, locally advanced, non-metastatic primary
             T3 or T4 adenocarcinoma of the rectum

          -  Patients must not have evidence of tumor outside of the pelvis including liver
             metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy

          -  Patients must not have intra-operative radiotherapy (IORT) or brachytherapy treatment
             to the pelvis

          -  The distal border of the tumor must be at or below the peritoneal reflection, defined
             as within 12 centimeters of the anal verge by proctoscopic examination

          -  Transmural penetration of tumor through the muscularis propria must be demonstrated by
             either of the following: computed tomography (CT) scan plus endorectal ultrasound, or
             a magnetic resonance imaging (MRI); an endorectal coil or pelvic MRI is allowed

          -  For the patient to be eligible, the surgeon must prospectively define the tumor as
             either initially resectable or potentially resectable after pre-operative
             chemoradiation; clinically resectable tumors are defined as completely resectable with
             negative margins based on routine examination of the non-anesthetized patient;
             patients whose tumors are not resectable are not eligible; before pre-operative (op)
             treatment, the surgeon should estimate and record the type of resection anticipated:
             pelvic exenteration, posterior pelvic exenteration, APR, LAR, or LAR/coloanal
             anastomosis

          -  Patients with tumors that are clinically fixed, clinical stage T4N0-2, M0 are eligible
             if it is believed that their tumors are potentially resectable after chemoradiation;
             based on the following:

               -  Clinically fixed tumors on rectal examination with tumor adherent to the pelvic
                  sidewall or sacrum

               -  Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the lack
                  of clear tissue plane will be considered evidence of fixation

               -  Hydronephrosis on CT scan or intravenous pyelogram (IVP) or ureteric or bladder
                  invasion as documented by cystoscopy and cytology or biopsy, or invasion into
                  prostate

               -  Vaginal or uterine involvement

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  A surgical evaluation must confirm patient's ability to tolerate the proposed surgical
             procedure

          -  Patients must have a caloric intake > 1500 kilocalories/day (d)

          -  Within 4 weeks prior to registration, the patient's absolute neutrophil count (ANC)
             level must be >= 1,500/mm^3

          -  Within 4 weeks prior to registration, the patients platelet level must be >=
             100,000/mm^3

          -  Within 4 weeks prior to registration, serum creatinine must be < 1.5 X upper limit of
             normal (ULN); if serum creatinine > 1.5 x ULN, then creatinine clearance must be >= 50
             mL/mm

          -  Within 4 weeks prior to registration, serum bilirubin must be =< 1.5 X ULN

          -  Within 4 weeks prior to registration, alkaline phosphatase (alk phos) must be < 2 x
             ULN

          -  Within 4 weeks prior to registration, serum glutamic oxaloacetic transaminase (SGOT)
             must be < 2 x ULN

          -  Carcinoembryonic antigen (CEA) must be determined prior to initiation of therapy

          -  Within 4 weeks prior to registration, urine protein/creatinine (UPC) ratio must be <
             1; patients with a ratio of >= 1 must undergo a 24-hour urine collection which must be
             an adequate collection and must demonstrate < 1 gram (gm) of protein in order to
             participate

          -  Within 4 weeks prior to registration, albumin must be >= 2 gm/dl

          -  Absence of clinical evidence of high-grade (lumen diameter < 1 cm) large bowel
             obstruction, unless diverting colostomy has been performed

          -  Eligible patients of reproductive potential (both sexes) must agree to use an accepted
             and effective method of contraceptive during study therapy and for at least 6 months
             after the completion of bevacizumab

          -  Women must not be pregnant or breast-feeding; all females of childbearing potential
             must have a serum pregnancy test to rule out pregnancy within 2 weeks of registration

          -  Patients must have had no prior chemotherapy for rectal cancer or pelvic irradiation
             therapy

          -  Patients with prior malignancies, including pelvic cancer, are eligible if they have
             been disease free for > 5 years; patients with prior in situ carcinomas are eligible
             provided there was complete removal

          -  Patients must have no active inflammatory bowel disease or other serious medical
             illness or disease that might limit the patient's ability to receive protocol therapy

          -  Patients with a history of cerebrovascular accident (CVA)/transient ischemic attack
             (TIA) at any time, or myocardial infarction/unstable angina within 12 months of study
             entry are not eligible

          -  Patients with > grade 1 peripheral neuropathy are not eligible

          -  Patients must have urine protein/creatinine (UPC) ratio of < 1.0; patients with a UPC
             ratio >= 1.0 must undergo a 24-hour urine collection, which must be an adequate
             collection and must demonstrate < 1 gm of protein in order to participate

          -  Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable
             regimen of anti-hypertensive therapy

          -  Patients with clinically significant peripheral vascular disease are not eligible

          -  Patients must not have any of the following:

               -  Unstable angina (within 12 months of study entry)

               -  New York Heart Association (NYHA) grade II or higher congestive heart failure

               -  Evidence of bleeding diathesis/coagulopathy

               -  Serious non-healing wound or bone fracture

          -  Patients with a history of the following within 28 days prior to registration are not
             eligible:

               -  Abdominal fistula

               -  Gastrointestinal perforation

               -  Intrabdominal abscess

          -  Patients with a history of the following within 28 days prior to day 0 (first
             treatment day) are not eligible:

               -  Major surgical procedure

               -  Open biopsy

               -  Significant traumatic injury

          -  Patients must not have core biopsy within 7 days prior to day 0 (first treatment day)

          -  Patients with prothrombin time (PT) (international normalized ratio [INR]) > 1.5 are
             not eligible, unless the patient is on full-dose anticoagulants; if so, the following
             criteria must be met for enrollment:

               -  The subject must have an in-range INR (usually between 2 and 3), be on a stable
                  dose of warfarin or on a stable dose of low molecular weight heparin

               -  The subject must not have active bleeding or a pathological condition that is
                  associated with a high risk of bleeding