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A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00642941
Recruitment Status : Completed
First Posted : March 25, 2008
Last Update Posted : April 4, 2017
Sponsor:
Collaborator:
Sarcoma Alliance for Research through Collaboration
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 19, 2008
First Posted Date  ICMJE March 25, 2008
Last Update Posted Date April 4, 2017
Actual Study Start Date  ICMJE December 18, 2007
Actual Primary Completion Date February 19, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2017)
  • Percentage of Participants with Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 [ Time Frame: Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression) ]
  • Progression-Free Survival (PFS) According to WHO Response Criteria at 18 weeks from Start of R2607 Treatment in Cohort 1 [ Time Frame: Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression) ]
  • Percentage of Participants with Adverse Events (AEs) in Cohort 1 and 2 [ Time Frame: Baseline up to 6 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 19, 2008)
  • Objective response rate [ Time Frame: Week 24, and every 12 weeks thereafter ]
  • Progression-free survival in patients with Ewing's sarcoma [ Time Frame: Week 18 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2017)
  • Duration of Response (DOR) According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • Time to Progression (TTP) According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • Overall Survival (OS) in Cohorts 2 to 8 [ Time Frame: Baseline until death (up to 6 years) ]
  • PFS According to WHO Response Criteria at 18 Weeks from Start of R1507 Treatment in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks until disease progression (up to 18 weeks) ]
  • PFS According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • Percentage of Participants with Complete or Partial Response According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • TTP According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • FFS According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • DOR According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • PFS According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
  • OS in Cohort 1 [ Time Frame: Baseline until death (up to 6 years) ]
  • Percentage of participants with AEs in all Cohorts [ Time Frame: Baseline up to 6 years ]
  • Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of R1507 [ Time Frame: Predose (0 hours [h]), end of 60-90 minutes infusion (EOI), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years) ]
  • Pharmacokinetics: Clearance (CL) of R1507 [ Time Frame: Predose (0 h), EOI (infusion over 60-90 minutes), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2008)
  • Duration of response, PFS. [ Time Frame: Week 18 ]
  • Overall PFS. [ Time Frame: Event driven ]
  • Overall objective response rate, response duration, overall PFS and overall survival in patients with Ewing's sarcoma. [ Time Frame: Event driven ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of R1507 in Participants With Recurrent or Refractory Sarcoma
Official Title  ICMJE A Phase II Trial of R1507, a Recombinant Human Monoclonal Antibody to the Insulin-Like Growth Factor-1 Receptor for the Treatment of Participants With Recurrent or Refractory Ewing's Sarcoma, Osteosarcoma, Synovial Sarcoma, Rhabdomyosarcoma and Other Sarcomas.
Brief Summary This study will evaluate the efficacy and safety of R1507 in participants with recurrent or refractory sarcoma. Eight cohorts of sarcoma participants will be studied in parallel. Cohort 1: Ewing's sarcoma primary cohort defined as participants who have relapsed less than or equal to (<=) 24 months from diagnosis, received at least two prior chemotherapy programs and are unresectable. Cohort 2: Ewing's sarcoma non-primary (secondary) cohort defined as participants who have relapsed greater than or equal to (>=) 24 months from diagnosis or have only received one prior chemotherapy program. Cohort 3: Expanded Ewing's sarcoma defined as participants with recurrent or relapse regardless of prior number of salvage regimens and regardless of time of relapse. Cohort 4: participants with osteosarcoma. Cohort 5: Participants with synovial sarcoma. Cohort 6: Participants with rhabdomyosarcoma Cohort 7: Participants with alveolar soft part sarcoma (7a), desmoplastic small round cell tumors (7b), extraskeletal myxoid chondrosarcoma (7c), clear cell sarcoma (7d), myxoid liposarcoma (7e). Cohort 8: Participants with unspecified sarcoma diagnosis. Participants in the expanded Ewing's sarcoma Cohort 3 will receive 27 milligrams (mg)/kilogram (kg) every 3 weeks intravenously (IV). All other participants will receive R1507 9 mg/kg IV weekly. The anticipated time on study treatment is until disease progression or unacceptable adverse events, withdrawal or death.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sarcoma
Intervention  ICMJE Drug: RG1507
Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.
Study Arms  ICMJE
  • Experimental: Cohort 1: Ewing's Sarcoma Primary Cohort
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.
    Intervention: Drug: RG1507
  • Experimental: Cohort 2: Ewing's Sarcoma Secondary Cohort
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.
    Intervention: Drug: RG1507
  • Experimental: Cohort 3: Ewing's Sarcoma Expanded Cohort
    Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.
    Intervention: Drug: RG1507
  • Experimental: Cohort 4: Osteosarcoma
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.
    Intervention: Drug: RG1507
  • Experimental: Cohort 5: Synovial Sarcoma
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.
    Intervention: Drug: RG1507
  • Experimental: Cohort 6: Rhabdomyosarcoma
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.
    Intervention: Drug: RG1507
  • Experimental: Cohort 7a: Alveolar Soft Part Sarcoma
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a includes individuals with alveolar soft part sarcoma.
    Intervention: Drug: RG1507
  • Experimental: Cohort 7b: Desmoplastic Small Round Cell Tumors.
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.
    Intervention: Drug: RG1507
  • Experimental: Cohort 7c: Extraskeletal Myxoid Chondrosarcoma
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.
    Intervention: Drug: RG1507
  • Experimental: Cohort 7d: Clear Cell Sarcoma
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.
    Intervention: Drug: RG1507
  • Experimental: Cohort 7e: Myxoid Liposarcoma
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.
    Intervention: Drug: RG1507
  • Experimental: Cohort 8: Diagnosis Not Specified
    Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
    Intervention: Drug: RG1507
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2017)
317
Original Estimated Enrollment  ICMJE
 (submitted: March 19, 2008)
180
Actual Study Completion Date  ICMJE February 19, 2014
Actual Primary Completion Date February 19, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • progressive, recurrent or refractory Ewing's sarcoma, or recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma, or other sarcomas of the following sub-types: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma and myxoid liposarcoma;
  • Cohort 3 only: age must be >= 2 and <= 21 years

Exclusion Criteria:

  • clinically significant unrelated systemic illness which would compromise the participant's ability to tolerate the investigational agent, or interfere with the study procedures or results;
  • known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies;
  • treatment (within the past 2 weeks) with pharmacologic doses of corticosteroids or other immunosuppressive agents;
  • current or prior therapy with insulin-like growth factor (IGF) inhibitor (monoclonal or specific kinase inhibitor);
  • history of solid organ transplant;
  • other malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer;
  • active central nervous system disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   France,   Germany,   Italy,   Netherlands,   Norway,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries Finland
 
Administrative Information
NCT Number  ICMJE NCT00642941
Other Study ID Numbers  ICMJE NO21157
SARC011
2007-003940-30 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Sarcoma Alliance for Research through Collaboration
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP