A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

Sarcoma Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00642941
• Other study ID #: NO21157
• Secondary ID: SARC0112007-0039
• Status: Terminated
• Phase: Phase 2
• Start date: December 18, 2007
• Est. completion date: February 19, 2014

Study information

• Verified date: January 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00615680

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 317
• Est. completion date: February 19, 2014
• Est. primary completion date: February 19, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma

Intervention

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.

Locations

Country	Name	City	State
Australia	Peter Maccallum Cancer Institute; Medical Oncology	Melbourne	Victoria
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
France	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
Germany	HELIOS Klinikum Bad Saarow; Klinik für Innere Medizin III	Bad Saarow
Germany	Uniklinik Mannheim; Sektion Chirurgische Onkologie & Thoraxchirurgie	Mannheim
Germany	University Hospital Tübingen	Tübingen
Italy	Istituti Ortopedici Rizzoli	Bologna	Emilia-Romagna
Italy	Istituto Nazionale Tumori, Sarcoma Unit	Milano	Lombardia
Netherlands	Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology	Rotterdam
Norway	Norwegian Radium Hospital	Oslo
Spain	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona
Sweden	Skånes University Hospital, Skånes Department of Onclology	Lund
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	UCL Hospital NHS Trust	London
United Kingdom	Christie Hospital NHS Trust	Manchester
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	NIH/NCI	Bethesda	Maryland
United States	Dana Farber Partners Can Ctr	Boston	Massachusetts
United States	Massachusetts General Hospital; Dana Farber Partnes Cancer Center	Boston	Massachusetts
United States	Albert Einstein College of Medical Pediatrics; Department of Pediatrics	Bronx	New York
United States	Carolinas Hematology Oncology Associates; Investigational Drug Services - Pharmacy	Charlotte	North Carolina
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	City of Hope National Medical Center	Duarte	California
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	UCLA School Of Medicine Mattel's Children's Hospital At UCLA; Division Of Hematology-Oncology	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Nebraska Methodist Hospital; Onc Hem West	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Pennsylvania Oncology Hema Asc	Philadelphia	Pennsylvania
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
United States	Huntsman Cancer Institute; Orthopedic Center	Salt Lake City	Utah
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

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Sarcoma Alliance for Research through Collaboration

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8	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.	Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression)
Primary	Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1	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.	Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression)
Primary	Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2		Baseline up to 6 years
Secondary	Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1	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.	Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Secondary	PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8	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.	Baseline, every 6 weeks until disease progression (up to 18 weeks)
Secondary	Percentage of Participants With AEs in Cohorts 3-8		Baseline up to 6 years
Secondary	Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8	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.	Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Secondary	Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8	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.	Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Secondary	Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 1 to 8	FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause.	Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Secondary	Overall Survival (OS) in Cohorts 1 to 8	OS was measured from the time of study registration to the date of death or was censored at the date of last contact.	Baseline until death (up to 6 years)
Secondary	PFS According to WHO Response Criteria in Cohorts 1 to 8	PFS is defined as the duration of time from start of treatment to time of objective progression or death.	Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Secondary	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)
Secondary	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)