Preoperative Combined Induction Chemotherapy With Capecitabine, Oxaliplatin, Bevacizumab and Radiotherapy

March 6, 2014 updated by: Austrian Breast & Colorectal Cancer Study Group

Preoperative Induction Chemotherapy in Combination With Bevacizumab Followed by Combined Chemoradiotherapy in Locally Advanced Rectal Cancer With High Risk of Recurrence- Phase II Pilot Study With Preoperative Administration of Capecitabine (Xeloda), Oxaliplatin and Bevacizumab (Avastin) Followed by Capecitabine (Xeloda) Plus Radiotherapy (RTx)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Induction chemotherapy combined with Radio chemotherapy:

Therapy start: within 28 days after bioptical diagnosis capecitabine 1000 mg/m2 bid during 14 days (d1-d14) , oxaliplatin 130 mg/m2 and bevacizumab 7.5 mg/kg body weight d1; repetition day 22 and 43 (3 cycles)

Combined Radiochemotherapy after 1 week of concluded 3rd cycle of induction chemotherapy:

Radiotherapy: 5 x 5 days 1.8 Gy; cumulative dose 45 Gy Chemotherapy: capecitabine 825mg/m² bid, on each radiation day during the first 4 weeks of RCTx

Surgery according to TME-criteria (total mesorectal excision) in compliance of an interruption of min. 14 days after RCTx

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Salzburg, Austria, 5020
        • Paracelsus Medical University Salzburg - Oncology
      • Vienna, Austria, 1090
        • Medical University of Vienna, General Hospital
    • Carinthia
      • St. Veit a. d. Glan, Carinthia, Austria, 9330
        • Hospital BHB St. Veit/Glan, Surgery
    • Styria
      • Graz, Styria, Austria, 8036
        • Medical University Graz, Oncology
    • Tyrol
      • Innsbruck, Tyrol, Austria, 6020
        • Medical University Innsbruck, Internal Medicine
    • Upper Austria
      • Wels, Upper Austria, Austria, 4600
        • Klinikum Wels-Grieskirchen
    • Vorarlberg
      • Feldkirch, Vorarlberg, Austria, 6807
        • State Hospital Feldkirch, Radiotherapy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18-80 years
  • Histologic confirmation of rectal adenocarcinoma 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 clearance > 50ml/min (Cockcroft and Gault formula))
  • Adequate liver function (bilirubin ≤1,5x ULN, GOT and GPT ≤3,5xULN)
  • 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

Exclusion Criteria:

  • Rectal carcinoma stage cT3 (> 5mm from the mesorectal fascia) all stages <cT3, M1
  • 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
  • Florid, 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 intrabdominal abscesses within 6 months prior to registration
  • Treatment with another investigational drug within 28 days prior to registration
  • Patients with malabsorption 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: induction chemotherapy + radiochemotherapy
preoperative induction chemotherapy in combination with bevacizumab followed by combined radiochemotherapy with capecitabine induction chemotherapy: starts within 28 days after bioptical diagnosis. All patients are administered with capecitabine (Xeloda®) 1000 mg/m2 bid during 14 days (d1-d14), oxaliplatin 130 mg/m2 and bevacizumab (Avastin®) 7.5 mg/kg body weight on day 1; repetition days 22 and 43 (3 cycles) Combined radiochemotherapy: starts at the earliest one week after concluded third cycle of induction chemotherapy. Radiotherapy takes place on 5 x 5 days (dose: 1.8 Gy; cumulative dose: 45 Gy). For chemotherapy patients are administered with capecitabine (Xeloda®) 825mg/m² bid, on each radiation day during the first 4 weeks of radiochemotherapy.
Drug: preoperative induction chemotherapy in combination with bevacizumab followed by combined radiochemotherapy with capecitabine
Therapy start: Capecitabine 1000mg/ m² bid during 14 days(d1-14), oxaliplatin 130mg/m² and Bevacizumab 7.5mg/kg body weight d1, repetition day 22 and 43 (3 cycles) Radiotherapy: Followed by 5 x 5 days 1.8 Gy after 1 week of concluded 3rd cycle of induction chemotherapy Chemotherapy: Capecitabine 825 mg/m2 bid (on each therapy day of first 4 therapy weeks)
Other Names:
  • Oxaliplatin
  • Avastin (bevacizumab)
  • Xeloda (capecitabine)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
termination of therapy
Time Frame: up to 17 weeks
before surgery (after conclusion of therapy phase)
up to 17 weeks
occurence of toxicity
Time Frame: up to 18-19 weeks
until timepoint of discharge of patient
up to 18-19 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
collection of response rate
Time Frame: up to week 18
T- and N-downstaging, pathological complete remission: measurement at the timepoint of surgery
up to week 18
post-surgery morbidity
Time Frame: after 18-19 weeks
according to Accordion; measurement at the timepoint of discharge of patient
after 18-19 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Austrian Breast & Colorectal Cancer Study Group

Collaborators

Hoffmann-La Roche

Investigators

  • Study Chair: Dietmar Öfner, MD, Head, Austrian Breast & Colorectal Cancer Study Group
  • Study Chair: Alexander de Vries, MD, Head, Austrian Breast & Colorectal Cancer Study Group
  • Study Chair: Wolfgang Eisterer, MD, Austrian Breast & Colorectal Cancer Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

September 13, 2011

First Submitted That Met QC Criteria

September 13, 2011

First Posted (Estimate)

September 14, 2011

Study Record Updates

Last Update Posted (Estimate)

March 7, 2014

Last Update Submitted That Met QC Criteria

March 6, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ABCSG R05
  • 2010-024354-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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