A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

Phase 2

Terminated

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

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
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 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 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 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 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 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 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 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 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 AEs in Cohorts 3-8	Baseline up to 6 years
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.
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): 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, 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
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City of Hope National Medical Center
🇺🇸Duarte, California, United States