A Study of R1507 in Participants With Recurrent or Refractory Sarcoma
- Conditions
- Sarcoma
- Interventions
- Drug: RG1507
- Registration Number
- NCT00642941
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 317
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 4: Osteosarcoma RG1507 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. Cohort 7d: Clear Cell Sarcoma RG1507 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. Cohort 2: Ewings Sarcoma Secondary Cohort RG1507 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. Cohort 3: Ewings Sarcoma Expanded Cohort RG1507 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. Cohort 1: Ewings Sarcoma Primary Cohort RG1507 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. Cohort 5: Synovial Sarcoma RG1507 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. Cohort 6: Rhabdomyosarcoma RG1507 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. Cohort 7a: Alveolar Soft Part Sarcoma RG1507 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. Cohort 7c: Extraskeletal Myxoid Chondrosarcoma RG1507 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. Cohort 7e: Myxoid Liposarcoma RG1507 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. Cohort 7b: Desmoplastic Small Round Cell Tumors. RG1507 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. Cohort 8: Diagnosis Not Specified RG1507 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 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.
Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1 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.
Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2 Baseline up to 6 years
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1 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.
PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 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.
Percentage of Participants With AEs in Cohorts 3-8 Baseline up to 6 years Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 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.
Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 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.
Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 1 to 8 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.
Overall Survival (OS) in Cohorts 1 to 8 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.
PFS According to WHO Response Criteria in Cohorts 1 to 8 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.
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of R1507 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 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)
Trial Locations
- Locations (41)
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
UCLA School Of Medicine Mattel's Children's Hospital At UCLA; Division Of Hematology-Oncology
🇺🇸Los Angeles, California, United States
Pennsylvania Oncology Hema Asc
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Nebraska Methodist Hospital; Onc Hem West
🇺🇸Omaha, Nebraska, United States
Huntsman Cancer Institute; Orthopedic Center
🇺🇸Salt Lake City, Utah, United States
HELIOS Klinikum Bad Saarow; Klinik für Innere Medizin III
🇩🇪Bad Saarow, Germany
Centre Oscar Lambret; Chir Cancerologie General
🇫🇷Lille, France
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
Istituti Ortopedici Rizzoli
🇮🇹Bologna, Emilia-Romagna, Italy
Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
🇳🇱Rotterdam, Netherlands
Uniklinik Mannheim; Sektion Chirurgische Onkologie & Thoraxchirurgie
🇩🇪Mannheim, Germany
Royal Marsden Hospital; Dept of Med-Onc
🇬🇧London, United Kingdom
Institut Bergonie; Oncologie
🇫🇷Bordeaux, France
Institut Curie; Oncologie Medicale
🇫🇷Paris, France
Stanford Comprehensive Cancer Center
🇺🇸Stanford, California, United States
University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Peter Maccallum Cancer Institute; Medical Oncology
🇦🇺Melbourne, Victoria, Australia
UCL Hospital NHS Trust
🇬🇧London, United Kingdom
Norwegian Radium Hospital
🇳🇴Oslo, Norway
Christie Hospital NHS Trust
🇬🇧Manchester, United Kingdom
Istituto Nazionale Tumori, Sarcoma Unit
🇮🇹Milano, Lombardia, Italy
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Skånes University Hospital, Skånes Department of Onclology
🇸🇪Lund, Sweden
Institut Gustave Roussy; Service Pediatrique
🇫🇷Villejuif, France
Hospital Sant Joan De Deu
🇪🇸Esplugues De Llobregas, Barcelona, Spain
University Hospital Tübingen
🇩🇪Tübingen, Germany
Centre Leon Berard; Departement Oncologie Medicale
🇫🇷Lyon, France
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Washington Cancer Institute; Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Kootenai Medical Center
🇺🇸Coeur d'Alene, Idaho, United States
NIH/NCI
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital; Dana Farber Partnes Cancer Center
🇺🇸Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Dana Farber Partners Can Ctr
🇺🇸Boston, Massachusetts, United States
Carolinas Hematology Oncology Associates; Investigational Drug Services - Pharmacy
🇺🇸Charlotte, North Carolina, United States
Albert Einstein College of Medical Pediatrics; Department of Pediatrics
🇺🇸Bronx, New York, United States
Oregon Health and Science University Cancer Institute
🇺🇸Portland, Oregon, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Texas Children's Cancer Center; Baylor College of Medicine
🇺🇸Houston, Texas, United States