ABCSG R05 Details

Pre-operative induction-chemotherapy in combination with bevacizumab followed by combined radio-chemotherapy of local progressive rectal cancer with high relapse risk – a phase-II-pilot-study with pre-operative capecitabine (Xeloda®), oxaliplatin and bevacizumab (Avastin®), followed by capecitabine (Xeloda®) plus radiotherapy (RTx).

Start:
4. QU/2011
End:
4. QU/2012

Contact ABCSG-Trial office

E-mail: info@abcsg.at
Phone: +43 1 408 92 30
Fax: +43 1 409 09 90

Design

ABCSG-R05- Design
Klick to enlarge

Primary objectives:

Feasibility and compatibility of preoperative induction chemotherapy (Capecitabine/Oxaliplatin) in combination with Bevacizumab (Avastin®) followed by combined radio chemotherapy with Capecitabine (Xeloda®) for patients with locally advanced rectal cancer.

Secondary objectives:

Evaluation of the response rate (downstaging of T- and N-stadium, rate of pathological complete remission), evaluation of post-operative morbidity after Accordion [17] on the discharge day (Appendix D).

Inclusion criteria:

  • Age 18 – 80 years
  • Bioptically proven rectal adenocarcinoma with cT3 (≤5mm removed from the mesorectal fascia)/cT4 (with primary curative intention) NxM0
  • No previous chemotherapy, no previous radiotherapy of pelvis or abdomen and no former rectal tumour resection
  • WHO Performance Status 0 – 2
  • sufficient bone marrow (leucocytes: ≥ 3000/µl, platelets: ≥ 100000/µl)
  • dequate liver function (bilirubin: ≤ 1.5 x upper limit, GOT and GPT ≤ 3.5 x upper limit)
  • adequate kidney function (creatinine: ≤ 1.5 mg/dl, creatinine-clearance: > 50 ml/min (cockroft and gault formula)
  • exclusion for pregnancy for women of childbearing age (negative urine- or serum pregnancy test)
  • The willingness of women of childbearing potential or procreative men to apply a recognized contraceptive method while and at least 3 months upon completion of the study
  • Life expectancy of at least 3 months
  • INR and aPTT ≤ 1.5 of the lower limit
  • Signed informed consent prior to randomization

Exclusion criteria:

  • Rectal carcinoma at cT3 stage (
  • Other malignant tumours within the last 5 years, except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
  • General contraindication respectively known hypersensitivity to Bevacizumab, Capecitabine and/or Oxaliplatin
  • non-malignant diseases as a result of radiotherapy or chemotherapy with Bevacicumab and Capeticabine or a rectum resection contraindicated: uncontrolled hypertension (systolic >150 mmHG and/or diastolic >100 mmHG) or clinically significant (i.e.: active) Cardiovascular diseases: CVA (cardiovascular accident)/cerebral apoplexy (≤ 6 months prior to randomization), myocardial infarction (≤ 6 months prior to randomization), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring treatment, hepatic affections, significant neurological and psychiatric disorders
  • Active, serious infection at randomization
  • Peripheral neuropathy (NCI CTCAE v4.0 ≥ grade 1)
  • Juristic limited legal capacity or indication of neurological or psychiatric diseases, in the doctor’s opinion, restricting the ability of the patient concerning compliance or observance of the protocol.
  • major surgical procedure within 28 days prior the start of the study, open wounds
  • serious injury, unhealed wounds or bone fracture
  • patient with spinal cord compression or metastases in the central nervous system
  • reference to bleeding diathesis or blood-clotting disorders
  • consumption of anticoagulant or thrombolyticsubstances, and/or aspirin > 325mg/d within 10 days prior to randomization
  • Current or recent (within 10 days prior to the beginning of the treatment) therapeutic treatment with fully dosed anticoagulants. A prophylactic treatment is permitted
  • previous thromboembolic or haemorrhagicevents within the last 6 months prior to randomization
  • previous abdominal fistula, GI perforations or intra-abdominal abscesses within the last 6 months prior to randomization
  • Treatment with study medication of another clinical trial within the last 28 days prior to randomization
  • Patients with malabsorption syndrome or difficulties in swallowing
  • Evidence for the lack of cooperation by patients
  • Pregnant or lactating women
  • Proteinuria: dipstick < 2+. If dipstick ≥ 2+ protein has to be measured in 24h-urine and may not be more than 1g/24h