A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

NCT ID: NCT00642941

Last Updated: 2021-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 317 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-18
• Study Completion Date: 2014-02-19

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.

Conditions

Sarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

RG1507

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sarcoma Alliance for Research through Collaboration

OTHER

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope National Medical Center

Duarte, California, United States

UCLA School Of Medicine Mattel's Children's Hospital At UCLA; Division Of Hematology-Oncology

Los Angeles, California, United States

Sarcoma Oncology Center

Santa Monica, California, United States

Stanford Comprehensive Cancer Center

Stanford, California, United States

Washington Cancer Institute; Washington Hospital Center

Washington D.C., District of Columbia, United States

Kootenai Medical Center

Coeur d'Alene, Idaho, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

NIH/NCI

Bethesda, Maryland, United States

Massachusetts General Hospital; Dana Farber Partnes Cancer Center

Boston, Massachusetts, United States

Dana Farber Partners Can Ctr

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Nebraska Methodist Hospital; Onc Hem West

Omaha, Nebraska, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Albert Einstein College of Medical Pediatrics; Department of Pediatrics

The Bronx, New York, United States

Carolinas Hematology Oncology Associates; Investigational Drug Services - Pharmacy

Charlotte, North Carolina, United States

Oregon Health and Science University Cancer Institute

Portland, Oregon, United States

Pennsylvania Oncology Hema Asc

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Texas Children's Cancer Center; Baylor College of Medicine

Houston, Texas, United States

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute; Orthopedic Center

Salt Lake City, Utah, United States

Peter Maccallum Cancer Institute; Medical Oncology

Melbourne, Victoria, Australia

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Institut Bergonie; Oncologie

Bordeaux, , France

Centre Oscar Lambret; Chir Cancerologie General

Lille, , France

Centre Leon Berard; Departement Oncologie Medicale

Lyon, , France

Institut Curie; Oncologie Medicale

Paris, , France

Institut Gustave Roussy; Service Pediatrique

Villejuif, , France

HELIOS Klinikum Bad Saarow; Klinik für Innere Medizin III

Bad Saarow, , Germany

Uniklinik Mannheim; Sektion Chirurgische Onkologie & Thoraxchirurgie

Mannheim, , Germany

University Hospital Tübingen

Tübingen, , Germany

Istituti Ortopedici Rizzoli

Bologna, Emilia-Romagna, Italy

Istituto Nazionale Tumori, Sarcoma Unit

Milan, Lombardy, Italy

Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology

Rotterdam, , Netherlands

Norwegian Radium Hospital

Oslo, , Norway

Hospital Sant Joan De Deu

Esplugues de Llobregas, Barcelona, Spain

Skånes University Hospital, Skånes Department of Onclology

Lund, , Sweden

UCL Hospital NHS Trust

London, , United Kingdom

Royal Marsden Hospital; Dept of Med-Onc

London, , United Kingdom

Christie Hospital NHS Trust

Manchester, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Italy; Netherlands; Norway; Spain; Sweden; United Kingdom

References

Asmane I, Watkin E, Alberti L, Duc A, Marec-Berard P, Ray-Coquard I, Cassier P, Decouvelaere AV, Ranchere D, Kurtz JE, Bergerat JP, Blay JY. Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas. Eur J Cancer. 2012 Nov;48(16):3027-35. doi: 10.1016/j.ejca.2012.05.009. Epub 2012 Jun 7.

Reference Type: DERIVED

PMID: 22682017 (View on PubMed)

Pappo AS, Patel SR, Crowley J, Reinke DK, Kuenkele KP, Chawla SP, Toner GC, Maki RG, Meyers PA, Chugh R, Ganjoo KN, Schuetze SM, Juergens H, Leahy MG, Geoerger B, Benjamin RS, Helman LJ, Baker LH. R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II Sarcoma Alliance for Research through Collaboration study. J Clin Oncol. 2011 Dec 1;29(34):4541-7. doi: 10.1200/JCO.2010.34.0000. Epub 2011 Oct 24.

Reference Type: DERIVED

PMID: 22025149 (View on PubMed)

Other Identifiers

SARC011

Identifier Type: -

Identifier Source: secondary_id

2007-003940-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NO21157

Identifier Type: -

Identifier Source: org_study_id

NCT00615680

Identifier Type: -

Identifier Source: nct_alias