A randomized phase II of bevacizumab, capecitabine and radiation therapy with or without oxaliplatin in the preoperative treatment of locally advanced rectal cancer - Axe Beam

Phase 1

• Conditions: locally advanced rectal cancer; MedDRA version: 9.1Level: LLTClassification code 10038049Term: Rectal cancer stage II; MedDRA version: 9.1Level: LLTClassification code 10038050Term: Rectal cancer stage III

• Registration Number: EUCTR2007-007177-23-BE
• Lead Sponsor: .Z. Gasthuisberg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-08
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Patient is at least 18 years of age.
• Patient’s body weight is = 120 kg.
• Histologically proven and evaluable (according to RECIST criteria) adenocarcinoma of the rectum (tumor = 12 cm from the anal verge).
• Patient is considered locally advanced by MRI; the following are eligible:
Tumor beyond mesorectal fascia (T4)
or
Tumor = 2 mm from mesorectal fascia
or
T3 tumor < 5 cm from anal verge

All radiology studies must be performed within 28 days prior to randomization.
• WHO PS = 2
• Adequate bone marrow, hepatic and renal function (assessed within 14 days prior to study entry)
• INR = 1.5 .
• Ability to swallow tablets.
• Presence of adequate contraception in fertile patients. Adequate methods of contraception are: intra-uterine device, hormonal contraception, condom use with spermicide.
• Written informed consent must be given according to ICH/GCP and national/local regulations

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Evidence of distant metastases.
• Prior chemotherapy or radiotherapy for rectal cancer.
• Pregnant or breastfeeding women.
• Presence of peripheral neuropathy > grade 1, according to CTCAE v3.0
• Presence of significant impairment of intestinal resorption (e.g. chronic diarrhea, inflammatory bowel disease).
• History or presence of allergy or any other adverse reaction to any of the study drugs or to any related compound, including hypersensitivity to chinese hamster ovary cell products or other recombinant human or humanised antibodies.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• History of arterial thrombo-embolic events, including transient ischemic attack (TIA), cerebro-vascular accident (CVA), and myocardial infarction within 6 months prior to randomisation. Presence of clinically significant peripheral artery disease or hemorrhagic events.
• Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication or history of myocardial infarction within the last 12 months.
• Presence of uncontrolled hypertension (defined as a systolic blood pressure more than 140 mmHg and diastolic blood pressure more than 90 mmHg). If the patient is unaware of his/her blood pressure and hypertension is detected, a cardiologic check-up prior to inclusion in this trial is mandatory.
• Treatment with full dose of anticoagulants (coumarine or heparin). Patients with prophylactic dose of low molecular weight heparin are eligible.
• Major surgical procedure or significant traumatic injury within 28 days before day 1 or patients in whom a surgical wound is not fully healed
• Presence of other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection.
• Previous or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and non-melanoma skin cancer.
• Presence of organ allografts requiring immunosuppressive therapy.
• Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine. Patients must be off these drugs for 4 weeks before enrollment.
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake.
• Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drug.
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: This phase II trial assesses the activity of bevacizumab (Avastin) in combination with capecitabine (Xeloda) and radiation therapy with or without oxaliplatin (Eloxatin) in the pre-operative treatment of locally advanced rectal cancer, followed by TME resection, in a multicenter setting. ;Primary end point(s): Pathologic Complete Response Rate;Secondary Objective: Secondary endpoints are:<br><br>Histopathologic negative CRM resection rate<br>Pathologic downstaging (yp T0-2 N0) rate<br>Tumor regression grade (TRG)<br>Clinical response rate (RECIST) at time of surgery<br>Quality of mesorectal excision<br>One month surgical complication rate<br>Toxicity<br>Loco-regional and distant recurrence rates<br>Progression-free and overall survival.<br>