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Trial record 1 of 1 for:    NCT00642941
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A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

This study has been completed.
Sponsor:
Collaborator:
Sarcoma Alliance for Research through Collaboration
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00642941
First received: March 19, 2008
Last updated: April 3, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Sarcoma
Drug: RG1507
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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) ]

Enrollment: 317
Actual Study Start Date: December 18, 2007
Study Completion Date: February 19, 2014
Primary Completion Date: February 19, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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: 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.
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.

  Eligibility

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
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
  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: NCT00642941

  Hide Study Locations
Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
UCLA School Of Medicine Mattel's Children's Hospital At UCLA; Division Of Hematology-Oncology
Los Angeles, California, United States, 90095-1752
Sarcoma Oncology Center
Santa Monica, California, United States, 90403
Stanford Comprehensive Cancer Center
Stanford, California, United States, 94305
United States, District of Columbia
Washington Cancer Institute; Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Idaho
Kootenai Medical Center
Coeur D'alene, Idaho, United States, 83814
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
NIH/NCI
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Massachusetts General Hospital; Dana Farber Partnes Cancer Center
Boston, Massachusetts, United States, 02114
Dana Farber Partners Can Ctr
Boston, Massachusetts, United States, 02115-6084
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Nebraska
Nebraska Methodist Hospital; Onc Hem West
Omaha, Nebraska, United States, 68114
United States, New York
Albert Einstein College of Medical Pediatrics; Department of Pediatrics
Bronx, New York, United States, 10467
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Carolinas Hematology Oncology Associates; Investigational Drug Services - Pharmacy
Charlotte, North Carolina, United States, 28203
United States, Oregon
Oregon Health and Science University Cancer Institute
Portland, Oregon, United States, 97239
United States, Pennsylvania
Pennsylvania Oncology Hema Asc
Philadelphia, Pennsylvania, United States, 19106
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
Texas Children's Cancer Center; Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute; Orthopedic Center
Salt Lake City, Utah, United States, 84112
Australia, Victoria
Peter Maccallum Cancer Institute; Medical Oncology
Melbourne, Victoria, Australia, 3000
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
France
Institut Bergonie; Oncologie
Bordeaux, France, 33076
Centre Oscar Lambret; Chir Cancerologie General
Lille, France, 59000
Centre Leon Berard; Departement Oncologie Medicale
Lyon, France, 69373
Institut Curie; Oncologie Medicale
Paris, France, 75231
Institut Gustave Roussy; Service Pediatrique
Villejuif, France, 94805
Germany
HELIOS Klinikum Bad Saarow; Klinik für Innere Medizin III
Bad Saarow, Germany, 15526
Uniklinik Mannheim; Sektion Chirurgische Onkologie & Thoraxchirurgie
Mannheim, Germany, 68167
Wilhelms University, Universitatsklinikum Munster, Medizinische Klinik und Poliklinik A
Münster, Germany, 481249
University Hospital Tübingen
Tübingen, Germany, 72076
Italy
Istituti Ortopedici Rizzoli
Bologna, Emilia-Romagna, Italy, 40136
Istituto Nazionale Tumori, Sarcoma Unit
Milano, Lombardia, Italy, 20133
Netherlands
Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
Rotterdam, Netherlands, 3075 EA
Norway
Norwegian Radium Hospital
Oslo, Norway, 0310
Spain
Hospital Sant Joan De Deu
Esplugues De Llobregas, Barcelona, Spain, 08950
Sweden
Skånes University Hospital, Skånes Department of Onclology
Lund, Sweden, 22185
United Kingdom
UCL Hospital NHS Trust
London, United Kingdom, NW1 2PG
Royal Marsden Hospital; Dept of Med-Onc
London, United Kingdom, SW3 6JJ
Christie Hospital NHS Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Hoffmann-La Roche
Sarcoma Alliance for Research through Collaboration
Investigators
Study Director: Clinical Trials Hoffmann-La Roche