OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX 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:
NCT00577031
First received: December 18, 2007
Last updated: July 21, 2015
Last verified: July 2015
  Purpose

This single arm study will evaluate the efficacy and safety of a first-line regimen of Avastin and XELOX (oxaliplatin + Xeloda) in patients with metastatic cancer of the colon or rectum. Patients will receive 21-day cycles of treatment, comprising Avastin 7.5mg/kg iv on day 1, oxaliplatin 130mg/m2 iv on day 1, and Xeloda 1000mg/m2 po twice daily on days 1-14, for a maximum of 6 months. Patients with stable disease or complete or partial response may continue on Avastin therapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.


Condition Intervention Phase
Colorectal Cancer
Drug: bevacizumab [Avastin]
Drug: Oxaliplatin
Drug: Xeloda
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Efficacy and Safety Study of Bevacizumab (Avastin®) in Combination With XELOX (Oxaliplatin Plus Xeloda®) for the First-line Treatment of Patients With Metastatic Cancer of the Colon or Rectum - 'OBELIX'

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-Free Survival (PFS): Percentage of Participants With Progressive Disease or Death [ Time Frame: Baseline and Day 1 of every cycle until disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented neither a relapse nor a new colorectal cancer had occurred. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  • PFS: Time to Event [ Time Frame: Baseline and Day 1 of every cycle until disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    PFS was defined as the time period in months from the start of study treatment to the first observation of disease progression or death from any cause, whichever occurred first. Data for participants with no tumor assessments after baseline but who were still alive at the time of the clinical cutoff were censored at Day 1. Participants who underwent surgery after experiencing a sufficient shrinkage of the tumor, had any relapse, new occurrence of colorectal cancer, or who died were all considered as having had an event. Participants who underwent surgery without any such event were censored at the date of the last tumor assessment that documented that neither a relapse nor a new colorectal cancer had occurred. Median PFS was estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) Among Participants in the ITT Population Who Had at Least 1 Post-Baseline Assessment [ Time Frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years ] [ Designated as safety issue: No ]
    The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as a greater than or equal to (≥) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

  • Percentage of Participants With a CR or PR Among Participants in the ITT Population [ Time Frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years ] [ Designated as safety issue: No ]
    CR and PR were defined using RECIST v1.0. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

  • Time to CR or PR Overall Response - Time to Event [ Time Frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years ] [ Designated as safety issue: No ]
    Time to overall response (CR or PR) was calculated as the time between the date of start of treatment until first documented response (CR or PR defined per RECIST v1.0). Participants who did not achieve CR or PR were censored at the date of progression, death, or at last adequate tumor assessment date. Median time to CR or PR overall response was estimated using the Kaplan-Meier method.

  • Percentage of Participants With a Best Overall Response of CR or PR During First Line Treatment [ Time Frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    CR and PR were defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

  • Duration of Overall Response Among Participants Whose Best Response Was CR or PR During First Line Treatment - Time to Event [ Time Frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    For participants with a best overall response of CR or PR, the duration of overall response was measured from the time that the criteria for CR or PR (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of overall response was estimated using the Kaplan-Meier method.

  • Percentage of Participants With a Stable Response During First Line Treatment [ Time Frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    Stable response defined as participants with a best overall response of CR, PR, or stable disease (SD), defined using RECIST v1.0 criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as a ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.

  • Duration of Stable Response [ Time Frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    For participants with a best overall response of CR, PR, or SD during first line treatment, the duration of stable response was measured from the time that the criteria for CR, PR, or SD (whichever occurred first) was met until the first date that progressive disease was objectively documented or until the date of death due to underlying cancer, whichever occurred first. Data for participants who did not have an event or who were alive without an objectively documented progressive disease were censored at the date of last adequate tumor assessment. Median duration of stable response was estimated using the Kaplan-Meier method.

  • Percentage of Participants With Treatment Failure [ Time Frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    Treatment-failure was defined as discontinuation of treatment for any reason, including the following qualifying events: death due to any cause, 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).

  • Time to Treatment Failure [ Time Frame: Baseline, every 3 weeks (every cycle) to disease progression or death up to 5 years ] [ Designated as safety issue: No ]
    Time to treatment-failure was defined as the time from the first day of treatment to discontinuation of treatment for any reason, including: death due to any cause, 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). For participants who did not experience a qualifying event, their data were censored at the earlier of either the date of last tumour assessment or the date of the last intake of study medication. Median time to treatment-failure was estimated using the Kaplan-Meier method.

  • Overall Survival: Percentage of Participants That Died Due to Any Cause [ Time Frame: Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive.

  • Overall Survival: Time to Event [ Time Frame: Baseline, Day 1 of every cycle to end-of-treatment, every 3 months during longer-term follow-up, or to death due to any cause up to 5 years ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of the first day of treatment until the date of death from any cause. If a participant was not known to have died, survival was censored at the last date the participant was known to be alive. Median overall survival was estimated using the Kaplan-Meier method.

  • Percentage of Participants Undergoing Surgical Intervention With Residual Disease Status Post-surgery [ Time Frame: At surgery, at least 6 to 8 weeks after last dose of bevacizumab up to 5 years ] [ Designated as safety issue: No ]
    The percentage of participants who underwent surgery during the study period with an evaluation of their disease status after surgery. The surgery during the study period was described by reason: curative, palliative, biopsy, other, or unknown. Residual disease status after surgery was described as: no residual disease due to radical surgery, presence of residual disease, unknown or not applicable.

  • Percentage of Participants With Best Overall Response of CR or PR by Kirsten Rat Sarcoma Viral Oncogene Homolog (K-Ras)/V-Raf Murine Sarcoma Viral Oncogene Homolog B (B-Raf) Mutation Status [ Time Frame: Baseline, every 9 weeks (every 3 cycles) until end of treatment, disease progression, or withdrawal up to 5 years ] [ Designated as safety issue: No ]

    The percentage of participants with a best overall response of CR or PR according to RECIST. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 mm). No new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

    The K-Ras and/or the B-Raf gene mutation status of participants was evaluated by the central laboratory using tumor samples. Wild-type participants did not have a mutation in either gene.


  • European Quality of Life 5 Dimension (EQ-5D) Raw-Index Score [ Time Frame: Baseline, every 9 weeks (every 3 cycles), at end-of-treatment up to 5 years ] [ Designated as safety issue: No ]
    Quality of life (QoL) assessments were used to derive pre-specified QoL scores according to the QoL manual "EQ-5D-3 Level (3L)" user guide for instrument version 4.0. The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The visual analog scale (VAS) component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The overall health score absolute changes were calculated for each participant as follows: (score at the end of treatment minus score at baseline). EQ-5D health states were converted into EQ-5D-3L raw index value by applying the scoring algorithm based on the European EQ-net VAS set. The raw index was chosen instead of rescaled index, since the questionnaire was used in order to obtain a quality of life assessment. The raw index scores ranged from 0 (worst health state) to 100 (best health state).


Enrollment: 205
Study Start Date: February 2008
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab [Avastin]
7.5mg iv on day 1 of each 3 week cycle
Drug: Oxaliplatin
130mg/m2 iv on day 1 of each 3 week cycle
Drug: Xeloda
1000mg/m2 po bid on days 1-14 of each 3 week cycle

  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;
  • locally advanced or metastatic colorectal cancer;
  • no previous treatment with chemotherapy for metastatic disease;
  • at least one measurable lesion.

Exclusion Criteria:

  • radiotherapy to any site within 4 weeks before study;
  • untreated brain metastases or primary brain tumors;
  • clinically significant cardiovascular disease;
  • chronic daily treatment with high dose aspirin (>325 mg/day);
  • other co-existing malignancies or malignancies diagnosed within last 5 years.
  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: NCT00577031

Locations
Italy
Bologna, Italy, 40138
Brescia, Italy, 25122
Cagliari, Italy, 09100
Cagliari, Italy, 09121
Caserta, Italy, 81100
Catanzaro, Italy, 88100
Cefalu, Italy, 90015
Fano, Italy, 61032
Firenze, Italy, 50139
Frattaminore, Italy, 80026
Grosseto, Italy, 58100
Ivrea, Italy, 10015
Latisana, Italy, 33053
Lecce, Italy, 73100
Legnago, Italy, 37045
Legnano, Italy, 20025
Macerata, Italy, 62100
Napoli, Italy, 80131
Negrar, Italy, 37024
Orbassano, Italy, 10043
Padova, Italy, 35128
Palermo, Italy, 90127
Palermo, Italy, 90146
Pavia, Italy, 27100
Reggio Calabria, Italy, 89100
Reggio Emilia, Italy, 42100
Rionero in Vulture, Italy, 85028
Roma, Italy, 00184
Roma, Italy, 00189
Roma, Italy, 00186
Roma, Italy, 00152
Salerno, Italy, 84131
San Giovanni Rotondo, Italy, 71013
Sondrio, Italy, 23100
Taormina, Italy, 98030
Torino, Italy, 10125
Torino, Italy, 10153
Verbania, Italy, 28921
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00577031     History of Changes
Other Study ID Numbers: ML21380
Study First Received: December 18, 2007
Results First Received: July 15, 2014
Last Updated: July 21, 2015
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Bevacizumab
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015