Preoperative Combined RadioChemo-Molecular Target Therapy With Capecitabine, Bevacizumab, and Radiotherapy

Phase 2

Terminated

• Conditions: Rectal Cancer
• Interventions: Drug: capecitabine, bevacizumab

• Registration Number: NCT00671645
• Lead Sponsor: Austrian Breast & Colorectal Cancer Study Group

Brief Summary

* feasibility and tolerance of preoperative therapy with Bevacizumab in combination with Capecitabine and radiotherapy for patients with locally advanced, locally operable rectal carcinoma

* collection of response rate (T- and M-downstaging, pathological complete remission)

Detailed Description

Combined RadioChemotherapy:

Therapy start: within 28 days after bioptical diagnosis

Radiotherapy: 5 x 5 days 1.8 Gy radiotherapy; cummulative dose 45 Gy

Chemotherapy: Capecitabin 825mg/m² bid, on each radiation day during the first 4 weeks RCTx

Molecular Targeted Therapy: Bevacizumab 5 mg/kg body weight; day 1, 15, 29 Operation due to TME adherence to a break of min. 42 to max. 56 days after the last application of bevacizumab

Study Timeline

• Study First Submitted: 2008-04-30
• Study First Submitted QC: 2008-04-30
• Study First Posted: 2008-05-05
• Study Start: 2008-07
• Primary Completion: 2009-02-27
• Study Completion: 2009-02-27
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-13
• Last Update Posted: 2020-10-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• age: 18 - 80
• bioptical confirmed adenocarcinoma of the rectum in T3NxM0 status. The tumor has to be basically surgically complete resectable (->R0).
• no former chemotherapy, radiotherapy of pelvis or abdomen and/or tumor resection of rectum carcinoma
• WHO performance status 0-2
• adequate bone marrow reserve (granulocytes >= 3.000/µl, absolute neutrophil >= 0 1,5 x 10 9/l thrombocytes: >= 100.000/µl, haemoglobin >= 10g/dl)
• adequate hepatic function (Bilirubin: <= 1.5 x ULN, GOT und GPT <= 2.5 x ULN)
• adequate renal function (creatinin: <= 1.25 mg/dl, creatinin-clearance: > 50 ml/min (Cockcroft and Gault formula)), proteinuria: dipstick < 2+. In case of dipstick > 2+ protein has to be measured in 24h urine and does not exceed more than 1g/24h)
• ability of intake of pills
• women of childbearing potential: exclusion of pregnancy (negative urin or serum pregnancy test)
• willingness of women of childbearing potential and accordingly of potent men to use approved contraceptives (e.g. birth-control pill, loop, condom) during and at least 3 month after conclusion of the study
• life expectancy of at least 3 month
• INR and aPTT < 1.5 ULN
• signed Informed Consent before recruitment

Exclusion Criteria

• failure of one inclusion criteria
• former radiotherapy of pelvis or abdomen
• former chemotherapy
• any other kind of malign tumor in the last 5 years
• any other kind of tumour in the last 5 years with exception of basal cell carcinoma of skin and cervix carcinoma in situ
• general contraindication or known hypersensitivity against Bevacizumab and/or Capecitabine
• non malign disease, if there is a contraindication with radiotherapy, or chemotherapy with Bevacizumab and Capecitabine, or a resection of rectum: uncontrolled hypertension (systolic > 150 mmHG and/or diastolic >100 mmHG) or clinical significant (e.g. active) cardiovascular disease: CVA (cardiovascular accident)/ cerebral apoplexy (< 6 months before recruitment), myocardial infarct (< 6 months before recruitment), instable angina pectoris, CHF with NYHA status II or higher, or treated serious arrhythmia, hepatic disease, significant neurologic or psychiatric disorders
• florid, serious infections at the time of recruitment
• peripheral neuropathy (NCI CTC >= Grade 1)
• legally limited contractual capability or evidence of neurological or psychiatric disease, if it will constrict the patients compliance in the opinion of the investigator
• evidence of lacking cooperation of the patient
• major intervention within 28 days before recruitment, open wounds
• serious injuries, unhealed wounds or fractures
• patients with spinal compressions or metastases in central nervous system
• evidence of bleeding diathesis or coagulation dysfunction
• actual intake of anticoagulant or thrombolytic agents, Aspirin > 325 mg/d or within 10 days before study start)
• actual or recent (within 10 days before recruitment) therapeutic therapy with fully-dosed anticoagulants. A prophylactic treatment is permitted.
• previous thromboembolic or hemorrhagic events within the last 6 months before recruitment
• previous abdominal fistulas, GI perforation or intra-abdominal abscess within the last 6 months
• treatment with other study medication within 28 days before recruitment
• patients with malabsorption syndrome or difficulties swallowing
• pregnant or breast feeding women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	capecitabine, bevacizumab	-

Primary Outcome Measures

Name	Time	Method
feasibility and tolerance of preoperative therapy with Bevacizumab in combination with Capecitabine and radiotherapy for patients with locally advanced, locally operable rectal carcinoma	descriptive evaluation

Secondary Outcome Measures

Name	Time	Method
collection of response rate (T- and M-downstaging, pathological complete remission)	descriptive evaluation

Trial Locations

Locations (10)

Hospital BHB St. Veit/Glan, Surgery; 🇦🇹 St. Veit/Glan, Carinthia, Austria

Hospital BHS Linz, Radiooncology; 🇦🇹 Linz, Upper Austria, Austria

State Hospital Feldkirch, Radiotherapy; 🇦🇹 Feldkirch, Vorarlberg, Austria

Medical University Vienna, Radiotherapy; 🇦🇹 Vienna, Austria

Medical University Graz, Oncology; 🇦🇹 Graz, Styria, Austria

State Hospital Leoben, Surgery; 🇦🇹 Leoben, Styria, Austria

Medical University Innsbruck, Internal Medicine; 🇦🇹 Innsbruck, Tyrol, Austria

State Hospital Salzburg-Paracelsius Medical University - Oncology; 🇦🇹 Salzburg, Austria

Klinikum Wels-Grieskirchen, Coop. Group; 🇦🇹 Wels, Upper Austria, Austria

Hospital BHB Vienna, Surgery; 🇦🇹 Vienna, Austria