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A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01227707
First received: October 22, 2010
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

This open-label study will assess the efficacy and safety of Avastin (bevacizumab) plus Xeloda (capecitabine) in combination with standard technique radiotherapy of the pelvic region in the neo-adjuvant setting in patients with locally advanced primary rectal cancer. Patients will receive 4 courses of Avastin at a dose of 5 mg/kg intravenously (iv) every 2 weeks and for 38 days Xeloda at dose of 825 mg/kg twice daily orally, plus radiation therapy. After surgery, adjuvant treatment with 5-fluorouracil/leucovorin and, at the discretion of the investigator, with Avastin 5 mg/kg iv every 2 weeks for at least 6 months will be given.


Condition Intervention Phase
Colorectal Cancer
Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Radiation: Radiation therapy
Procedure: Mesorectal excision
Drug: 5-fluorouracil
Drug: leucovorin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study to Assess the Effect of Combination Treatment With Avastin and Xeloda, Plus Pre-operative Standard Radiotherapy, on Response Rate in Patients With Locally Advanced Rectal Cancer.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Pathological Complete Response (pCR) [ Time Frame: 6 to 8 weeks following completion of neoadjuvant treatment ] [ Designated as safety issue: No ]
    pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected.


Secondary Outcome Measures:
  • Percentage of Participants by Primary Tumor (T), Regional Lymph Nodes (N), and Distant Metastasis (M) Clinical Stage at Baseline and at the End of Neo-Adjuvant Treatment (NAT) [ Time Frame: Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment) ] [ Designated as safety issue: No ]
    The frequencies of clinical tumor stage T (0, 1, 2, 3, 4, or X), regional lymph nodes stage N (0, 1, 2, 3, or 4), and distant metastasis clinical stage M (0, 1, or X) at baseline and at the end of NAT were assessed. The frequencies of pathological tumor stage T and regional lymph nodes stage N at surgery were evaluated. The clinical tumor and lymph node status was assessed by clinical examination, endosonography, and/or rectosigmoidoscopy, and pelvic and abdomen computerized tomography (CT) scan or magnetic resonance imaging (MRI). Response to treatment had to be assessed within 6 weeks after end of treatment by using the same techniques performed at baseline.

  • Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure [ Time Frame: 6 to 8 weeks after completion of study treatment ] [ Designated as safety issue: No ]
  • Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment [ Time Frame: BL and within 6 weeks after the completion of study treatment ] [ Designated as safety issue: No ]
    Percentage of participants with CR was evaluated as the proportion of participants with complete response for the target and non-target lesions, separately, at the end of NAT according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target lesions or all non-target lesions and normalization of tumor marker levels.

  • Percentage of Participants With an Overall Response of CR at the End of Neoadjuvant Treatment [ Time Frame: BL and within 6 weeks after the completion of study treatment ] [ Designated as safety issue: No ]
    Percentage of participants with an overall response of CR was evaluated as the proportion of participants with CR for the target and non-target lesions plus absence of new lesions at the end of NAT according to RECIST. CR was defined as disappearance of all target lesions, all non-target lesions, and normalization of tumor marker levels.

  • Percentage of Participants With New Lesions at the Primary Tumor Site at the End of Neoadjuvant Treatment [ Time Frame: BL and within 6 weeks after the completion of study treatment ] [ Designated as safety issue: No ]
    The percentage of participants with new lesions located at the primary tumor site were evaluated at the end of NAT.

  • Percentage of Participants With Relapse During Follow-Up [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months ] [ Designated as safety issue: No ]
    The percentage of participants with local and/or regional relapse during follow-up. New lesions located at rectum or at colon or at lymph node detected at the end of NAT were evaluated as local and/or regional relapse.

  • Disease-Free Survival (DFS) - Percentage of Participants With an Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months ] [ Designated as safety issue: No ]
    DFS was defined as the time from treatment start date to the date of first progression of disease or date of death due to any cause.

  • DFS - Time to Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months ] [ Designated as safety issue: No ]
    The time in months from date of start-of-treatment to the date of event defined as the first documented disease progression or death due to any cause. If a participant did not have an event, the time was censored at the date of last adequate tumor assessment. DFS was estimated using the Kaplan-Meier method.

  • Overall Survival (OS) - Percentage of Participants With an Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ] [ Designated as safety issue: No ]
    OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive.

  • OS - Time to Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ] [ Designated as safety issue: No ]
    OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive. OS was estimated using the Kaplan-Meier method.

  • Time to Disease Progression (TTP) - Percentage of Participants With an Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ] [ Designated as safety issue: No ]
    TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer.

  • TTP - Time to Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ] [ Designated as safety issue: No ]
    TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer. TTP was estimated using the Kaplan-Meier method.


Enrollment: 43
Study Start Date: November 2005
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: bevacizumab [Avastin]
5 mg/kg intravenously every 2 weeks, 4 cycles
Drug: capecitabine [Xeloda]
825 mg/m2 twice daily orally, 38 days
Radiation: Radiation therapy
Total dose of 45 Gy over 38 days
Procedure: Mesorectal excision
6-8 weeks after completion of neoadjuvant treatment
Drug: bevacizumab [Avastin]
Post-surgery adjuvant treatment at the discretion of the investigator: 5 mg/kg iv every 2 weeks for at least 6 months
Drug: 5-fluorouracil
Post-surgery adjuvant therapy: bolus of 400mg/m2 iv plus iv infusion of 600 mg/m2 on Days 1 and 2 of each 2-week cycle for 6 months
Drug: leucovorin
Post-surgery adjuvant treatment: 100 mg/m2 iv on Days 1 and 2 of each 2-week cycle for 6 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >=18 years of age
  • Patients with confirmed rectal cancer who are subject to surgery and would benefit from pre-operative combined chemo-radiotherapy
  • Measurable and/or evaluable lesions according to RECIST criteria
  • EOCG performance status 0-1

Exclusion Criteria:

  • Prior radiotherapy or chemotherapy for rectal cancer
  • Untreated brain metastases or spinal cord compression or primary brain tumors
  • Chronic daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration
  • Co-existing malignancies, or malignancies diagnosed within the last 5 years, with the exception of basal and squamous cell cancer, or cervical cancer in situ.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227707

Locations
Italy
Ancona, Italy, 60121
Bologna, Italy, 40139
Cuneo, Italy, 12100
Genova, Italy, 16132
Napoli, Italy, 80131
Paola, Italy, 87027
Pisa, Italy, 56100
Roma, Italy, 00135
Siena, Italy, 53100
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01227707     History of Changes
Other Study ID Numbers: ML18522
Study First Received: October 22, 2010
Results First Received: May 28, 2014
Last Updated: July 24, 2014
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Capecitabine
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014