A Study of Avastin (Bevacizumab) and Oxaliplatin Plus Xeloda (Capecitabine) in Patients With Advanced Colorectal Cancer.

Phase II Study of the Combination of Bevacizumab (rhuMab VEGF) and Oxaliplatin Plus Capecitabine (XELOX) in Patients With Advanced Colorectal Cancer

This study will assess the efficacy and safety of treatment with the combination Avastin (bevacizumab) 5mg/kg iv every 2 weeks, Xeloda (capecitabine) 1000 mg po b.i.d. on Days 1-14 of every 28-day cycle and oxaliplatin 40mg/m2 iv weekly in patients with inoperable locally advanced or metastatic colorectal cancer. The anticipated time on study treatment is until disease progression.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: bevacizumab [Avastin]; Drug: capecitabine [Xeloda]; Drug: oxaliplatin

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Aviano, Italy, 33081
  • Fano, Italy, 61032
  • Palermo, Italy, 90146
  • Rimini, Italy, 47900
  • Roma, Italy, 00135
  • Torino, Italy, 10126

Participation Criteria

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:

• Adult patients >=18 years of age
• Locally advanced or metastatic colorectal cancer
• No previous treatment with chemotherapy for metastatic disease
• Measurable and/or evaluable lesions

Exclusion Criteria:

• Radiotherapy within 4 weeks before study
• Untreated brain metastases or primary brain tumors
• Chronic, daily treatment with high-dose aspirin (>325mg/day)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: bevacizumab [Avastin]; 5 mg/kg intravenously every 14 days; Drug: capecitabine [Xeloda]; 1000 mg/m2 orally b.i.d. , Days 1 - 14 of every 28-day cycle; Drug: oxaliplatin; 40 mg/m2 iv weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR)	Percentage of participants with OR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met.	Baseline, every 3 months to progression of disease or end of study (up to 24 months)
Percentage of Participants by Best Overall Response	Best response recorded from the start of treatment until disease progression. Based on assessment of CR, PR, stable disease (SD), or progressive disease (PD), according to RECIST. CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: ≥30% decrease under baseline of the sum of the LD diameters of all target lesions. CR and PR persist on repeat imaging study at least 4 weeks after initial documentation. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Reference is the smallest sum LD. PD: at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum longest diameter recorded or the appearance of one or more new lesions.	Baseline, every 3 months to progression of disease or end of study (up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response - Percentage of Participants With an Event by 24 Months	Duration of overall response (CR or PR) was calculated only for participants of the ITT population whose best overall response was CR or PR based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR or PR status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact.	Baseline, every 3 months to progression of disease or end of study (up to 24 months)
Duration of Response	Duration of overall response (CR or PR) was calculated for participants of the ITT population whose best overall response was CR or PR based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR or PR status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact. Mean time to event was estimated using the Kaplan-Meier method.	Baseline, every 3 months to progression of disease or end of study (up to 24 months)
Duration of Stable Disease - Percentage of Participants With an Event by 24 Months	Duration of stable response (CR, PR, or stable disease [SD]) was calculated only for participants of the ITT population whose best overall response was CR, PR, or SD based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR, PR, or SD status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact.	Baseline, every 3 months to progression of disease or end of study (up to 24 months)
Duration of Stable Disease	Duration of stable response (CR, PR, or SD) was calculated only for participants of the ITT population whose best overall response was CR, PR, or SD based on RECIST criteria. Duration of overall response was defined as the time from the date of the first assessment of CR, PR, or SD status until the date of progression or death. Data for participants who were alive without any objectively documented disease progression at the end of the study were censored as of the date of last contact. Mean time to event was estimated using the Kaplan-Meier method.	Baseline, every 3 months to progression of disease or end of study (up to 24 months)
Time to Treatment Failure (TTF) - Percentage of Participants With an Event by 24 Months	TTF was defined as the time in months from Day 1 until discontinuation of treatment for any reasons. These reasons included: death due to any cause, treatment toxicity (adverse event), insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent).	Baseline, every month to end of treatment (up to 24 months)
Time to Treatment Failure	TTF was defined as the time in months from Day 1 until discontinuation of treatment for any reasons. These reasons included: death due to any cause, treatment toxicity (adverse event), insufficient therapeutic response (progression of disease), failure to return (lost to follow-up), refusing treatment (participant non-compliance), being unwilling to cooperate and withdrawing consent (participant withdrew consent). Mean TTF was estimated using the Kaplan-Meier method.	Baseline, monthly to end of study (up to 24 months)
Time to Progression (TTP) - Percentage of Participants With an Event by 24 Months	TTP was defined as the time time in months from Day 1 until the date of first documented progressive disease, or death due to any cause. Data for participants who were alive without disease progression at the end of study, or who were non-responder participants (without tumor assessment after baseline) were censored at Day 1.	Baseline, monthly to end of study (up to 24 months)
Time to Progression	TTP was defined as the time in months from Day 1 until the date of first documented progressive disease, or death due to any cause. Data for participants who were alive without disease progression at the end of study, or who were non-responder participants (without tumor assessment after baseline) were censored at Day 1. Mean TTP was estimated using the Kaplan-Meier method.	Baseline, monthly to end of study (up to 24 months)
Overall Survival (OS) - Percentage of Participants With an Event by 24 Months	OS was defined as the time in months from Day 1 until the date of death due to any cause. Data for participants who were alive at the end of the study were censored at the date of the last available follow-up visit.	Baseline, monthly to end of study (up to 24 months)
Overall Survival	OS was defined as the time in months from Day 1 until the date of death due to any cause. Data for participants who were alive at the end of the study were censored at the date of the last available follow-up visit. Mean OS was estimated using the Kaplan-Meier method.	Baseline, monthly to end of study (up to 24 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: July 7, 2010
• First Submitted That Met QC Criteria: July 8, 2010
• First Posted (Estimate): July 9, 2010

Study Record Updates

• Last Update Posted (Estimate): August 15, 2014
• Last Update Submitted That Met QC Criteria: July 24, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: ML18523

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No