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Trial record 2 of 3 for:    rhabdomyosarcoma and bevacizumab

A Study of Avastin (Bevacizumab) in Combination With Standard Chemotherapy in Children and Adolescents With Sarcoma.

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00643565
First received: March 20, 2008
Last updated: January 15, 2016
Last verified: January 2016
  Purpose
This open-label two-arm study will assess the safety and efficacy of a combination of bevacizumab + standard chemotherapy with standard chemotherapy alone as active comparator in childhood and adolescent patients with metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma. Patients will be randomized to receive bevacizumab + standard chemotherapy or standard chemotherapy alone. Treatment will consist of 9 x 3-week cycles of induction treatment (standard chemotherapy with or without bevacizumab 7.5 mg/kg iv on day 1 of each cycle) followed by 12 x 4-week cycles of maintenance treatment (standard chemotherapy with or without bevacizumab 5 mg/kg iv on days 1 and 15 of each cycle). The anticipated time on study treatment is 1-2 years.

Condition Intervention Phase
Sarcoma
Drug: Standard chemotherapy
Drug: bevacizumab [Avastin]
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: An Open-label, Multi-center, Randomized Study of the Safety and Effect on Event-free Survival of Bevacizumab in Combination With Standard Chemotherapy in Childhood and Adolescent Patients With Metastatic Rhabdomyosarcoma and Non-rhabdomyosarcoma Soft Tissue Sarcoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Who Experienced Event-Free Survival (EFS) Events as Per Independent Review Committee (IRC) Assessment [ Time Frame: Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years up to data cut-off date 31 May 2015) ] [ Designated as safety issue: No ]
    EFS events included tumor progression (IRC assessed), no evidence of response after 3 cycles of induction (derived from IRC assessment), second primary cancer, or death due to any cause. Data for participants who had not experienced an event by the time of clinical cut-off were censored at the date of the last disease assessment prior to the clinical cut-off date. Data for participants who did not have any post-baseline disease assessments were censored at the time of randomization. Tumor progression was defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) as at least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions, or evidence of clinical progression and unequivocal progression of existing non-target lesions.

  • EFS Duration as Per IRC Assessment [ Time Frame: Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years up to data cut-off date 31 May 2015) ] [ Designated as safety issue: No ]
    EFS was defined as the time between randomization and occurrence of EFS event. EFS events are described in Outcome Measure 1. Median EFS was estimated using Kaplan-Meier estimates and 95% confidence intervals (CI) for median was computed using the method of Brookmeyer and Crowley.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response Prior to First Local Therapy Assessed by RECIST v1.0 Criteria [ Time Frame: Screening up to approximately 6.75 years (data cut-off date 31 May 2015) ] [ Designated as safety issue: No ]
    Objective response prior to first local therapy (surgery and/or radiotherapy) was defined as complete response (CR) or partial response (PR) determined on two consecutive occasions >/=4 weeks apart. Tumor response was assessed as per IRC using RECIST v1.0. CR was defined as disappearance of all target and non-target lesions. If immunocytology was available, no disease was to be detected by that methodology. PR was defined as at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study entry.

  • Percentage of Participants Who Experienced EFS Events Among Participants Who Had Objective Response [ Time Frame: Screening up to approximately 6.75 years (data cut-off date 31 May 2015) ] [ Designated as safety issue: No ]
    EFS events was described in Outcome Measure 1 and Outcome Measure 3.

  • Duration of Response [ Time Frame: Screening up to approximately 6.75 years (data cut-off date 31 May 2015) ] [ Designated as safety issue: No ]
    Duration of Response was defined as time between first objective response and the occurrence of an EFS event (described in Outcome Measure 1). Objective response was defined in Outcome Measure 3. Median duration of response was estimated using Kaplan-Meier estimates and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • Percentage of Participants Who Died [ Time Frame: Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years up to data cut-off date 31 May 2015) ] [ Designated as safety issue: No ]
  • Overall Survival Duration [ Time Frame: Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years up to data cut-off date 31 May 2015) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Median overall survival was estimated using Kaplan-Meier estimates and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • Area Under the Curve at Steady State (AUCss) of Bevacizumab [ Time Frame: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase ] [ Designated as safety issue: No ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUCss is expressed in milligrams times days per milliliter (mg*day/mL).

  • Volume of Distribution of Bevacizumab [ Time Frame: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks) ] [ Designated as safety issue: No ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

  • Half-Life of Bevacizumab [ Time Frame: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks) ] [ Designated as safety issue: No ]
    Half-life is the time measured for the plasma concentration to decrease by one half.

  • Clearance of Bevacizumab [ Time Frame: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks) ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL is expressed in milliliters per day (mL/day).


Enrollment: 154
Study Start Date: July 2008
Estimated Study Completion Date: May 2019
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Standard chemotherapy
As prescribed
Drug: bevacizumab [Avastin]
7.5 mg/kg iv on day 1 of 9 x 3-week cycles, followed by 5 mg/kg iv on days 1 and 15 of each 4-week cycle
Active Comparator: 2 Drug: Standard chemotherapy
As prescribed

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • childhood and adolescent patients aged >/=6 months to 18 years of age
  • metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma
  • adequate bone marrow function
  • adequate renal and liver function
  • adequate blood clotting

Exclusion Criteria:

  • previous malignant tumors
  • tumor invading major blood vessels
  • prior systemic anti-tumor treatment
  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: NCT00643565

  Show 61 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00643565     History of Changes
Other Study ID Numbers: BO20924  2007-005017-19 
Study First Received: March 20, 2008
Results First Received: December 7, 2015
Last Updated: January 15, 2016
Health Authority: France:AFSSAPS/DEMEB

Additional relevant MeSH terms:
Bevacizumab
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on January 18, 2017