Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer
Condition: Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: Radiation therapy; Oxaliplatin; Raltitrexed; levofolinic acid; 5-fluorouracil; Bevacizumab
Intervention description: Radiation therapy will be administered at the total dose of 45 Gy, given with five weekly fractions over a period of 5 weeks. The daily fraction dose will be 1.8 Gy; 100 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy); 2.5 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1) , an additional 2 cycles of chemotherapy will be given after radiation therapy); 250 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy); 800 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy); will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage (statistical design) with the classical schedule (for patients with resectable organ metastases (M1), one additional administration of bevacizumab will be given after radiation therapy)
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin; Raltitrexed; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: locally advanced; high risk; preoperative therapy

Summary:

      The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and
      bevacizumab before surgery in patients with locally advanced rectal cancer (LARC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically or cytologically confirmed diagnosis of locally advanced
             rectal cancer (LARC) at high risk of recurrence (T4, N+, T3N0 with tumor located in
             the lower third of the rectum and/or circumferential resection margin (CRM) £5 mm), or
             LARC with resectable organ metastasis (M1).

          -  Age 18 years or older

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

          -  Life expectancy of at least 12 weeks

          -  Measurable and/or evaluable (resectable organ metastasis)lesions according to RECIST
             criteria

          -  Neutrophils > 1500 and Platelets > 100,000 /L

          -  Total bilirubin < or = 1.5 time the upper-normal limits (UNL) of the Institutional
             normal values and ASAT (SGOT) and/or ALAT (SGPT) < or = 2.5 x UNL, or < or = 5 x UNL
             in case of liver metastases, alkaline phosphatase < or = 2.5 x UNL, or < or = 5 x UNL
             in case of liver metastases.

          -  Creatinine clearance > 50 mL/min or serum creatinine < or = 1.5 x UNL

          -  Urine dipstick of proteinuria < 2+. Patients discovered to have > or = 2+ proteinuria
             on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must
             demonstrate < or = 1 g of protein/24 hr.

          -  Written informed consent.

          -  Patients must be accessible for treatment and follow up. Patients registered on this
             trial must be treated and followed at the participating Center

        Exclusion Criteria:

          -  Prior radiotherapy or chemotherapy for rectal cancer.

          -  Untreated brain metastases or spinal cord compression or primary brain tumours

          -  History or evidence upon physical examination of CNS disease unless adequately treated
             (e.g., seizure not controlled with standard medical therapy or history of stroke).

          -  History of inflammatory bowel disease and/or acute/subacute bowel occlusion

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Uncontrolled hypertension

          -  Clinically significant (i.e. active) cardiovascular disease, for example
             cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), unstable
             angina, New York Heart Association (NYHA) grade II or greater congestive heart
             failure, serious cardiac arrhythmia requiring medication

          -  Current or recent (within 10 days prior to study treatment start) ongoing treatment
             with anticoagulants for therapeutic purposes.

          -  Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications
             known to predispose to gastrointestinal ulceration.

          -  Treatment with any investigational drug within 30 days prior to enrolment.

          -  Patients with known allergy to Chinese hamster ovary cell proteins, or any of the
             components of the study medications

          -  Other co-existing malignancies or malignancies diagnosed within the last 5 years with
             the exception of basal and squamous cell carcinoma or cervical cancer in situ

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study treatment start, or anticipation of the need for major surgical
             procedure during the course of the study.

          -  Pregnant or lactating women. Women of childbearing potential with either a positive or
             no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at
             least 12 months to be considered of non-childbearing potential. Sexually active males
             and females (of childbearing potential) unwilling to practice contraception during the
             study.