Study of Bevacizumab Alone or Combined With Capecitabine and Oxaliplatin as Support Therapy in Metastatic Colorectal Cancer Patients

February 19, 2013 updated by: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Randomized, Multicenter, Phase III Study, to Evaluate the Efficacy and Safety of Bevacizumab Alone or Combined With Capecitabine and Oxaliplatin as Support Therapy After Initial Chemotherapy Treatment With Capecitabine, Oxaliplatin and Bevacizumab in Metastatic Colorectal Cancer Patients

The purpose of this study is to compare the free time to disease progression of combination therapy with capecitabine, oxaliplatin and bevacizumab until disease progression versus capecitabine, oxaliplatin and bevacizumab for 6 cycles followed by bevacizumab until disease progression or a premature drop out of the study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to compare the free time to disease progression of combination therapy with capecitabine, oxaliplatin and bevacizumab until disease progression versus capecitabine, oxaliplatin and bevacizumab for 6 cycles followed by bevacizumab until disease progression or a premature drop out of the study.

Study Type

Interventional

Enrollment (Actual)

480

Phase

  • Phase 3

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

  • Spain
      • Madrid, Spain, 28046
        • Spanish Cooperative Group for Gastrointestinal Tumour Therapy

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written informed consent given.
  • Patients who are able to understand the study request.
  • Men and women > or = 18 years, not hospitalized.
  • Outpatients with ECOG performance status ≤ 2.
  • Histologically confirmed diagnosis of colorectal cancer (CRC) patients with metastasis.
  • Presence of at least one detectable lesion in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • Life expectancy of greater than 3 months.
  • Men and women potentially fertile using an effective contraceptive method

Exclusion Criteria:

  • Patients who have been treated with bevacizumab previously.

  • Received any systemic treatment previously to treat an advanced or metastatic disease

    • Adjuvant or neoadjuvant treatment to non-metastatic disease is allowed, provided that it has been finished at least 6 months before the initial study treatment.
    • If the patient has been treated with adjuvant therapy previously, it is not allowed to be included in the study in case of disease progression during treatment or for 6 months after the end of treatment.
    • If radiotherapy has not been administered in the lesion selected for the study, previous radiotherapy is allowed, unless progression of those injuries can be documented in the radiated field, as long as the end of the treatment has been finished at least 4 weeks before study initiation.
    • Previous surgical procedure of stage IV disease is allowed.
  • Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or this study indication, unless there has been a disease-free interval of at least 2 years.
  • History or evidence upon physical examination of central nervous system
  • History of psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake.
  • Clinically significant cardiovascular disease (active).
  • Patients who have undergone myocardial infarction or cerebrovascular accident 6 months prior to randomisation will be excluded.
  • Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medications.
  • Patients subjected to allogeneic transplant and request immunotherapy.
  • Bone fracture not healed, wounds or severe ulcers.
  • Known hemorrhagic diathesis or coagulopathy.
  • Uncontrolled and severe intercurrent infections or other severe and uncontrolled concomitant diseases.
  • Moderate or severe renal impairment (creatinine clearance < 30 ml/min [calculated according to Cockroft-Gault formula] or serum creatinine ≥ 2 mg/dl or 177 μmol/l).

  • Any of the following laboratory values:

    • Absolute neutrophil count (ANC) ≤ 1.5 x 10^9/l.
    • Platelet count ≤ 100 x 10^9/l.
    • Hemoglobin ≤ 9 g/dl.
    • International Normalized Ratio (INR) ≥ 1.5.
    • Total bilirubin ≥ 1.5 x upper limit of normal (ULN).
    • ALT and/or AST ≥ 2.5 x ULN or ≥ 5 x ULN (in case of hepatic metastasis).
    • Alkaline phosphatase > 2.5 x ULN or 5 x ULN (in case of hepatic metastasis), or > 10 x ULN (in case of bone metastasis).
  • History of unexpected serious adverse events to fluoropyrimidine treatments or known dihydropyrimidine dehydrogenase (DPD) deficiency.
  • Patients subjected to major surgical procedure or open biopsy; or patients have had significant traumatic injuries 28 days before the initial study treatment; or patients with a major surgical procedure planned during the study period.
  • Fine needle aspiration biopsy 7 days before study initiation.
  • Use of full dose of oral or parenteral anticoagulants (at least 10 days before the initial study treatment) or thrombolytic agents. Low dose of warfarin is allowed, with an INR ≤ 1.5.
  • Subjects requiring chronic use of high dose aspirin (> 325 mg/day) or non-steroidal anti-inflammatory treatment (those known to inhibit platelet function at doses used to treat chronic inflammatory diseases).
  • Pregnant or lactating women.
  • Patients with known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies; or to any excipients of bevacizumab formulation; or to any other study drugs.
  • Received any investigational drug or agent/procedure, i.e. participation in another treatment trial within 30 days of randomisation.
  • Evidence of another disease, metabolic malfunction, discovery in a physical examination or in a clinical laboratory test to result in reasonable suspicion of a condition or disease that contraindicates investigational medicine use or exposes the patient to high risk treatment complications.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
XELOXA
Drug: XELOXA
XELOXA Bevacizumab: 7,5 mg/kg, day 1 Oxaliplatino: 130 mg/m2 ; day 1 Capecitabine: 1000 mg/m2 bid, oral, day 1-14 One cycle every 3 weeks
Experimental: 2
XELOXA-A
Drug: XELOXA-A

XELOXA-A Bevacizumab: 7,5 mg/kg, day 1 Oxaliplatino: 130 mg/m2 ; day 1 Capecitabine: 1000 mg/m2 bid, oral, day 1-14 during 6 cycles followed by Bevacizumab until disease progression or premature drop out of study.

One cycle every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the free time to disease progression
Time Frame: 2006-2012
2006-2012

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 2006-2012
2006-2012
Overall response rate
Time Frame: 2006-2012
2006-2012
Time to onset of response
Time Frame: 2006-2012
2006-2012
Duration of response
Time Frame: 2006-2012
2006-2012
Treatment cycles number
Time Frame: 2006-2012
2006-2012
Number of patients who need medicine dose reduction
Time Frame: 2006-2012
2006-2012
adverse events
Time Frame: 2006-2012
2006-2012
Prognostic and predictive factor of Circulating endothelial cells (CEC) and circulating tumors cells (CTC) baseline and after 3 cycle
Time Frame: 2006-2012
2006-2012
Prognostic factor of the K-Ras gene mutation
Time Frame: 2006-2012
2006-2012

Collaborators and Investigators

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

Sponsor

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Collaborators

Sanofi
Roche Pharma AG

Investigators

  • Study Chair: Enrique Aranda, MD; phD, Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)
  • Study Chair: Eduardo Díaz-Rubio, MD; phD, Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)

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

July 1, 2006

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

June 9, 2006

First Submitted That Met QC Criteria

June 9, 2006

First Posted (Estimate)

June 12, 2006

Study Record Updates

Last Update Posted (Estimate)

February 20, 2013

Last Update Submitted That Met QC Criteria

February 19, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TTD-05-02
  • EudraCT Nº: 2005-003325-67

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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