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

• ClinicalTrials.gov Identifier: NCT01131078
• Recruitment Status: Completed
• First Posted: May 26, 2010
• Results First Posted: December 31, 2014
• Last Update Posted: June 4, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: Bevacizumab [Avastin]; Drug: Capecitabine; Drug: Irinotecan	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 306 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: June 2005
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: November 2012

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.
2. Time to Progression (TTP) [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
   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 :

1. Percentage of Participants Who Died [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
   Overall survival is defined as the time from date of randomization until death from any cause
2. Overall Survival [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
   Overall survival is defined as the time from date of randomization until death from any cause; Kaplan-Meier estimates were used for analysis.
3. Percentage of Participants With Treatment Failure [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
   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.
4. Time to Treatment Failure [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
   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.
5. 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 ]
   The failure event was defined as tumor progression excluding deaths due to any reason.
6. Time to Progression Excluding Deaths [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
   The failure event was defined as tumor progression excluding deaths due to any reason. Kaplan-Meier estimates were used for analysis.
7. 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 ]
   The failure event was defined as tumor progression excluding only deaths not related to underlying cancer.
8. 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 ]
   The failure event was defined as tumor progression excluding only deaths not related to underlying cancer. Kaplan-Meier estimates were used for analysis.
9. 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 ]
   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;
10. 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 ]
    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;
11. Percentage of Participants With Stable Disease [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
    Stable disease rate was the proportion of participants who achieved CR, PR, or SD.
12. Percentage of Participants With Progressive Disease Within 12 Weeks From Start of Treatment [ Time Frame: Randomization, Weeks 3, 6 and 9, and 12 ]
    Early progression was the proportion of participants with progressive disease within 12 weeks from the start of treatment.
13. Duration of Overall Response [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
    Duration of overall response included participants who achieved a CR or PR.
14. Duration of Stable Disease (SD) [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death ]
    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.
15. Duration of Overall Complete Response [ Time Frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: ML18524
• First Posted: May 26, 2010
• Results First Posted: December 31, 2014
• Last Update Posted: June 4, 2015
• Last Verified: June 2015

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; Bevacizumab; Capecitabine; Irinotecan; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors