Phase II pilot study of a preoperative induction chemotherapy in combination with Bevacizumab followed by combined radiochemotherapy for patients with locally advanced rectal carcinoma

• Conditions: locally advanced rectal cancer with high risk of recurrence; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-024354-11-AT
• Lead Sponsor: ABCSG (Austrian Breast & Colorectal Cancer Study Group)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-25
• Last Update Posted: 9 December 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

•Age 18-80 years
•Histologic confirmation of rectal andenocarcinoma stage cT3 (= 5mm to the mesorectal fascia)/cT4( primary curative intention)NxM0
•No former chemotherapy, no former radiotherapy of the pelvic, no former tumour resection of a rectal carcinoma
•General condition WHO grade 0-2
•Adequate bone marrow reserve ( leucocytes =3 000/µl, thrombocytes =100 000/µl)
•Adequate renal function (creatinine = 1,5 mg/dl, creatinine clearence > 50ml/min (Cockroft and Gault formula))
•Adequate liver function (bilirubin =1,5x ULN, GOT and GPT =3,5x ULN)
•Exclusion of pregnancy for women with childbearing potential (negative pregnancy test urine or serum)
•Female patients with childbearing potential and male patients that are not surgically sterile must be practicing a medically acceptable contraceptive regimen while on study treatment until 3 months after the end of the study (e.g. oral contraceptives, condom, intrauterine device)
•Life expectancy of at least 3 months
•INR and aPTT = 1,5 x LLN
•Provision of signed informed consents before registration

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

•Rectal carcinoma stage cT3 (> 5mm from the mesorectal fascia) all stages •Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
•General contraindication or known hypersensitivity against Bevacizumab, Capecitabine and Oxaliplatin
•Not malignant diseases for which treatment with radiotherapy, resection of the rectum and treatment with chemotherapy (Bevacizumab, Capecitabine) is contraindicated:
uncontrolled hypertension (systolic > 150 mmHG and/or diastolic > 100 mmHG) or clinically significant (e.g. active) cardiovascular diseases: CVA (cardiovascular accident)/ apoplectic insult (= 6 months prior to registration), myocardial infarction (= 6 months prior to registration), unstable angina pectoris, CHF(congestive heart failure) with NYHA (New York heart Association) Grade II or higher, cardiac arrhythmia requiring therapy, hepatic diseases, significant neurologic or psychiatric disorders
•Florids, serious infection at registration
•Peripheral neuropathy (NCI CTCAE v 4.0 = grade 1)
•Juridically limited contractual capability, indication of neurological or psychiatric disease which constrains upon investigators opinion the patients capability to adhere to the study routines
•Major surgical procedure within 28 days prior start of the study, open wounds
•Significant traumatic injury, bone fracture, unhealed wounds
•Patients with spinal cord compression or metastases in the central nervous system
•Indication of bleeding diathesis or coagulopathy
•Intake of anticoagulant or thrombolytic agents and/or Aspirin > 325 mg/d within 10 days prior to registration
•Current or recent (within 10 days prior to treatment start) therapy with full dosed anticoagulants. Preventive therapy is allowed.
•Previous thromboembolic or haemorrhagic events within 6 months prior to registration
•Previous abdominal fistulas, gastro-intestinal perforation or intra-abdominal abscesses within 6 months prior to registration
•Treatment with another investigational drug within 28 days prior to registration
•Patients with malabsorbtion syndrome or difficulties in swallowing
•Indication of poor compliance of the patient
•Pregnant or breast-feeding women
•Proteinuria: Dipstick <2+. If the Dipstick is =2+ protein has to be estimated in the 24 hours urine. The value should not be higher then 1g/24 hours.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: feasibility and tolerance of a preoperative induction chemotherapy in combination with Bevacizumab followed by combined radiochemotherapy with Capecitabine for patients with locally advanced rectal carcinoma;Secondary Objective: Assessment of the respond rate (R0 rate, downstaging of the T- and N-stage), evaluation of the postoperative morbidity according to Accordeon at the day of release from the inpatient stay;Primary end point(s): termination of therapy, occurrence of toxicity;Timepoint(s) of evaluation of this end point: - termination of therapy: before surgery (after conclusion of therapy phase)<br>- occurence of toxicity: until the timepoint of discharge of patient

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): downstaging of the T- and N-stage, occurrence of pathological complete remission, post-surgery morbidity according to Accordion;Timepoint(s) of evaluation of this end point: - downstaging of the T- and N-stage, occurrence of pathological complete remission: at the timepoint of surgery<br>- morbitdity: at the timepoint of discharge of patient