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A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

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ClinicalTrials.gov Identifier: NCT00642941
Recruitment Status : Terminated (The study was closed to further enrollment due to the decision by the Sponsor to discontinue development of R1507.)
First Posted : March 25, 2008
Results First Posted : February 3, 2021
Last Update Posted : February 3, 2021
Sponsor:
Collaborator:
Sarcoma Alliance for Research through Collaboration
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
The study was primarily designed to determine objective response, progression-free survival (PFS), and the safety and tolerability of R1507 in participants with recurrent or refractory Ewing's sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas including alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma.

Condition or disease Intervention/treatment Phase
Sarcoma Drug: RG1507 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 317 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : December 18, 2007
Actual Primary Completion Date : February 19, 2014
Actual Study Completion Date : February 19, 2014


Arm Intervention/treatment
Experimental: Cohort 1: Ewings 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.
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.

Experimental: Cohort 2: Ewings 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.
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.

Experimental: Cohort 3: Ewings 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.
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.

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.
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.

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.
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.

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.
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.

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.
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.

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.
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.

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.
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.

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.
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.

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.
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.

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.
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.




Primary Outcome Measures :
  1. 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) ]
    Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is >=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

  2. Progression-Free Survival (PFS) Rate 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) ]
    The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response) at 18 weeks from start of treatment.

  3. Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2 [ Time Frame: Baseline up to 6 years ]

Secondary Outcome Measures :
  1. 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) ]
    Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is >=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

  2. PFS Rate 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) ]
    The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response at 18 weeks) from start of treatment.

  3. Percentage of Participants With AEs in Cohorts 3-8 [ Time Frame: Baseline up to 6 years ]
  4. Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
    The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is >=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

  5. Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
    TTP is defined as the time from date of randomization until objective tumor progression. According to the WHO Response Criteria, objective tumor progression is > 25% increase in the area of one or more measurable lesions or the appearance of new lesions.

  6. Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 1 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
    FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause.

  7. Overall Survival (OS) in Cohorts 1 to 8 [ Time Frame: Baseline until death (up to 6 years) ]
    OS was measured from the time of study registration to the date of death or was censored at the date of last contact.

  8. PFS According to WHO Response Criteria in Cohorts 1 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]
    PFS is defined as the duration of time from start of treatment to time of objective progression or death.

  9. 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) ]
  10. 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) ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00642941


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Sarcoma Alliance for Research through Collaboration
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00642941    
Obsolete Identifiers: NCT00615680
Other Study ID Numbers: NO21157
SARC011
2007-003940-30 ( EudraCT Number )
First Posted: March 25, 2008    Key Record Dates
Results First Posted: February 3, 2021
Last Update Posted: February 3, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms