Clinical trial NCT00642941: A Study of R1507 in Participants With Recurrent or Refractory Sarcoma
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sarcoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Sarcoma Alliance for Research through Collaboration
First posted: 2008-03-25
Enrollment: 317
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8
timeFrame: Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression)
measure: Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1
timeFrame: Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression)
measure: Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2
timeFrame: Baseline up to 6 years
Secondary outcomes:
measure: Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1
timeFrame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
measure: PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8
timeFrame: Baseline, every 6 weeks until disease progression (up to 18 weeks)
measure: Percentage of Participants With AEs in Cohorts 3-8
timeFrame: Baseline up to 6 years
measure: Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8
timeFrame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
measure: Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8
timeFrame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
measure: Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 1 to 8
timeFrame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
measure: Overall Survival (OS) in Cohorts 1 to 8
timeFrame: Baseline until death (up to 6 years)
measure: PFS According to WHO Response Criteria in Cohorts 1 to 8
timeFrame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of R1507
timeFrame: 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)
measure: Pharmacokinetics: Clearance (CL) of R1507
timeFrame: 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)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA School Of Medicine Mattel's Children's Hospital At UCLA; Division Of Hematology-Oncology
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Stanford
country: United States
facility: Stanford Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Washington Cancer Institute; Washington Hospital Center
state: District of Columbia
city: Coeur d'Alene
country: United States
facility: Kootenai Medical Center
state: Idaho
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Bethesda
country: United States
facility: NIH/NCI
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital; Dana Farber Partnes Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Partners Can Ctr
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Omaha
country: United States
facility: Nebraska Methodist Hospital; Onc Hem West
state: Nebraska
city: Bronx
country: United States
facility: Albert Einstein College of Medical Pediatrics; Department of Pediatrics
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Hematology Oncology Associates; Investigational Drug Services - Pharmacy
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hema Asc
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Cancer Center; Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute; Orthopedic Center
state: Utah
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute; Medical Oncology
state: Victoria
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Bordeaux
country: France
facility: Institut Bergonie; Oncologie
city: Lille
country: France
facility: Centre Oscar Lambret; Chir Cancerologie General
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Paris
country: France
facility: Institut Curie; Oncologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy; Service Pediatrique
city: Bad Saarow
country: Germany
facility: HELIOS Klinikum Bad Saarow; Klinik für Innere Medizin III
city: Mannheim
country: Germany
facility: Uniklinik Mannheim; Sektion Chirurgische Onkologie & Thoraxchirurgie
city: Tübingen
country: Germany
facility: University Hospital Tübingen
city: Bologna
country: Italy
facility: Istituti Ortopedici Rizzoli
state: Emilia-Romagna
city: Milano
country: Italy
facility: Istituto Nazionale Tumori, Sarcoma Unit
state: Lombardia
city: Rotterdam
country: Netherlands
facility: Erasmus Mc - Daniel Den Hoed Kliniek; Medical Oncology
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Esplugues De Llobregas
country: Spain
facility: Hospital Sant Joan De Deu
state: Barcelona
city: Lund
country: Sweden
facility: Skånes University Hospital, Skånes Department of Onclology
city: London
country: United Kingdom
facility: UCL Hospital NHS Trust
city: London
country: United Kingdom
facility: Royal Marsden Hospital; Dept of Med-Onc
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.