Clinical trial NCT00671645: Preoperative Combined RadioChemo-Molecular Target Therapy With Capecitabine, Bevacizumab, and Radiotherapy
Official title: Preoperative Combined RadioChemo-MolecularTargetTherapy of the Locally Advanced Rectum Carcinoma (cT3NxM0) - a Phase II Pilot Study With Preoperative Application of Capecitabine, Bevacizumab and Radiotherapy (RTx)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: pilot study
rectal
carcinoma
phase II
preoperative
RadioChemo
molecular
target
therapy
T3
ABCSG
TAKO
R04
08
Lead sponsor: Austrian Breast & Colorectal Cancer Study Group
Sponsor class: NETWORK
Collaborators: name: Hoffmann-La Roche
First posted: 2008-05-05
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: feasibility and tolerance of preoperative therapy with Bevacizumab in combination with Capecitabine and radiotherapy for patients with locally advanced, locally operable rectal carcinoma
timeFrame: descriptive evaluation
Secondary outcomes:
measure: collection of response rate (T- and M-downstaging, pathological complete remission)
timeFrame: descriptive evaluation
Other outcomes:
Locations:
city: St. Veit/Glan
country: Austria
facility: Hospital BHB St. Veit/Glan, Surgery
state: Carinthia
city: Graz
country: Austria
facility: Medical University Graz, Oncology
state: Styria
city: Leoben
country: Austria
facility: State Hospital Leoben, Surgery
state: Styria
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Internal Medicine
state: Tyrol
city: Linz
country: Austria
facility: Hospital BHS Linz, Radiooncology
state: Upper Austria
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen, Coop. Group
state: Upper Austria
city: Feldkirch
country: Austria
facility: State Hospital Feldkirch, Radiotherapy
state: Vorarlberg
city: Salzburg
country: Austria
facility: State Hospital Salzburg-Paracelsius Medical University - Oncology
city: Vienna
country: Austria
facility: Hospital BHB Vienna, Surgery
city: Vienna
country: Austria
facility: Medical University Vienna, Radiotherapy
Study officials:
affiliation: Austrian Breast & Colorectal Cancer Study Group
name: Dietmar Oefner, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Austrian Breast & Colorectal Cancer Study Group
name: Alexander de Vries, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ABCSG, TAKO
name: Wolfgang Eisterer, MD
role: PRINCIPAL_INVESTIGATOR
References: