A Study of Avastin (Bevacizumab) in Combination Chemotherapy in Patients With Metastatic Cancer of the Colon or Rectum

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01131078
First received: April 20, 2010
Last updated: June 2, 2015
Last verified: June 2015
  Purpose
A study of Avastin (bevacizumab) in combination chemotherapy in patients with metastatic cancer of the colon or rectum. The anticipated time on study treatment is until disease progression.

Condition Intervention Phase
Colorectal Cancer
Drug: Bevacizumab [Avastin]
Drug: Capecitabine
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label Study Comparing the Effect of 3 Chemotherapy Regimens Containing Avastin on Time to Disease Progression in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Disease Progression or Death [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.

  • Time to Progression (TTP) [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    TTP is defined as the time from date of randomization until objective tumor progression or death due to any cause. It includes deaths and thus can be correlated to overall survival.


Secondary Outcome Measures:
  • Percentage of Participants Who Died [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from date of randomization until death from any cause

  • Overall Survival [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from date of randomization until death from any cause; Kaplan-Meier estimates were used for analysis.

  • Percentage of Participants With Treatment Failure [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Treatment failure is defined as discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent.

  • Time to Treatment Failure [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Time to treatment failure is defined as a composite endpoint measuring time from date of randomization to discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent. Analysis was performed using Kaplan-Meier estimates.

  • Percentage of Participants With Progression Excluding Deaths [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    The failure event was defined as tumor progression excluding deaths due to any reason.

  • Time to Progression Excluding Deaths [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    The failure event was defined as tumor progression excluding deaths due to any reason. Kaplan-Meier estimates were used for analysis.

  • Percentage of Participants With Progression Excluding Deaths Not Related to Underlying Cancer [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    The failure event was defined as tumor progression excluding only deaths not related to underlying cancer.

  • Time to Progression Excluding Deaths Not Related to Underlying Cancer [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    The failure event was defined as tumor progression excluding only deaths not related to underlying cancer. Kaplan-Meier estimates were used for analysis.

  • Percentage of Participants by Best Overall Response [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Best overall response is defined as the best response recorded from the date of randomization until disease progression or recurrence. Complete response (CR): at least 2 determinations of CR at least 4 weeks apart before progression; Partial response (PR): at least 2 determinations of PR at least 4 weeks apart before progression; Stable disease (SD): at least one SD assessment; Progressive Disease (PD): Disease progression or death due to underlying cancer. CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions; PD: At least 20% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of longest diameter of all target lesions or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for CR or PR or increase in lesions;

  • Percentage of Participants With a Best Overall Response of CR or PR [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions;

  • Percentage of Participants With Stable Disease [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Stable disease rate was the proportion of participants who achieved CR, PR, or SD.

  • Percentage of Participants With Progressive Disease Within 12 Weeks From Start of Treatment [ Time Frame: Randomization, Weeks 3, 6 and 9, and 12 ] [ Designated as safety issue: No ]
    Early progression was the proportion of participants with progressive disease within 12 weeks from the start of treatment.

  • Duration of Overall Response [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Duration of overall response included participants who achieved a CR or PR.

  • Duration of Stable Disease (SD) [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ] [ Designated as safety issue: No ]
    Duration of SD was calculated as the number of months the participants remained in CR, PR or SD. Kaplan-Meier estimates were used for analysis.

  • Duration of Overall Complete Response [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years ] [ Designated as safety issue: No ]
    Duration of complete response was calculated as the time in months from the date of randomization to the date of first documentation of CR. Kaplan-Meier estimates were used for analysis.


Enrollment: 306
Study Start Date: June 2005
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2)
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Drug: Bevacizumab [Avastin]
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle.
Other Name: Avastin
Drug: Capecitabine
Capecitabine was administered orally at a doses of 1000 or 1250, mg/m^2 twice daily (Day 2 to 15) or as 650 mg/m^2 twice daily on Days 1 to 21.
Drug: Irinotecan
Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks.
Experimental: Bevacizumab + Capecitabine (1250 mg/m^2)
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle in combination with capecitabine administered orally at 1250 mg/m^2 twice daily (Day 1 to 14). Cycle length was 3 weeks with 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal.
Drug: Bevacizumab [Avastin]
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle.
Other Name: Avastin
Drug: Capecitabine
Capecitabine was administered orally at a doses of 1000 or 1250, mg/m^2 twice daily (Day 2 to 15) or as 650 mg/m^2 twice daily on Days 1 to 21.
Experimental: Bevacizumab + Capecitabine (650 mg/m^2)
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 Week cycle in combination with capecitabine administered orally at 650 mg/m^2 twice daily (Day 1 to 21). Cycle length was 3 weeks with 3 weeks of capecitabine treatment without interruptions. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal.
Drug: Bevacizumab [Avastin]
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle.
Other Name: Avastin
Drug: Capecitabine
Capecitabine was administered orally at a doses of 1000 or 1250, mg/m^2 twice daily (Day 2 to 15) or as 650 mg/m^2 twice daily on Days 1 to 21.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients >=18 years of age;
  • colon or rectal cancer, with metastases;
  • >=1 measurable lesion.

Exclusion Criteria:

  • previous systemic treatment for advanced disease;
  • radiotherapy to any site within 4 weeks before study;
  • daily aspirin (>325 mg/day), anticoagulants, or other medications known to predispose to gastrointestinal ulceration;
  • co-existing malignancies or malignancies diagnosed within last 5 years (except basal 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: NCT01131078

Locations
Italy
Paola, Calabria, Italy, 87027
Benevento, Campania, Italy, 82100
Napoli, Campania, Italy, 80136
Bologna, Emilia-Romagna, Italy, 40138
Carpi, Emilia-Romagna, Italy, 41012
Piacenza, Emilia-Romagna, Italy, 29100
Latisana, Friuli-Venezia Giulia, Italy, 33053
Udine, Friuli-Venezia Giulia, Italy, 33100
Latina, Lazio, Italy, 04100
Roma, Lazio, Italy, 00168
Roma, Lazio, Italy, 00186
Brescia, Lombardia, Italy, 25123
Busto Arsizio, Lombardia, Italy, 21052
Casalpusterlengo, Lombardia, Italy, 20071
Cremona, Lombardia, Italy, 26100
Gorgonzola, Lombardia, Italy, 20064
Lecco, Lombardia, Italy, 23900
Legnago, Lombardia, Italy, 37045
Mantova, Lombardia, Italy, 46100
Milano, Lombardia, Italy, 20121
Milano, Lombardia, Italy, 20133
Milano, Lombardia, Italy, 20142
Milano, Lombardia, Italy, 20162
Pavia, Lombardia, Italy, 27100
Saronno, Lombardia, Italy, 21047
Sondrio, Lombardia, Italy, 23100
Treviglio, Lombardia, Italy, 24047
Varese, Lombardia, Italy, 21100
Ancona, Marche, Italy, 60121
Novara, Piemonte, Italy, 28100
Torino, Piemonte, Italy, 10153
Cagliari, Sardegna, Italy, 09100
Catania, Sicilia, Italy, 95100
Palermo, Sicilia, Italy, 90127
Firenze, Toscana, Italy, 50139
Grosseto, Toscana, Italy, 58100
Pisa, Toscana, Italy, 56100
Prato, Toscana, Italy, 59100
Bolzano, Trentino-Alto Adige, Italy, 39100
Terni, Umbria, Italy, 05100
Camposampiero, Veneto, Italy, 35012
Este, Veneto, Italy, 35042
Montecchio Maggiore, Veneto, Italy, 36075
Negrar, Veneto, Italy, 37024
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01131078     History of Changes
Other Study ID Numbers: ML18524 
Study First Received: April 20, 2010
Results First Received: December 19, 2014
Last Updated: June 2, 2015
Health Authority: ITALY: Agenzia Italiana del Farmaco

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Irinotecan
Bevacizumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 27, 2016