Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma
NCT ID: NCT01614795
Last Updated: 2018-12-11
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE2
46 participants
INTERVENTIONAL
2012-06-18
2014-04-01
Brief Summary
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Detailed Description
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I. To determine the objective response rate to the combination of cixutumumab and temsirolimus in patients with relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, or non-rhabdomyosarcoma soft tissue sarcoma.
II. To further describe the toxicities (including dose-limiting toxicities) of cixutumumab and temsirolimus administered on this schedule.
SECONDARY OBJECTIVES:
I. To assess the progression-free survival for patients treated in each disease stratum with this drug combination.
II. To assess the incidence of insulin-like growth factor 1 receptor (IGF-1R), insulin receptor, ERK, RON, and mammalian target of rapamycin (mTOR) pathway activation in archival tumor material, and correlate with response.
III. To evaluate minimal residual disease and IGF-1R tumor cell expression in the blood and bone marrow of Ewing sarcoma patients using flow cytometry.
OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (osteosarcoma vs Ewing sarcoma/PNET vs rhabdomyosarcoma vs non-rhabdomyosarcoma soft tissue sarcoma).
Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.
Archived tumor tissue samples from most recent biopsy are collected and analyzed for IGF-1R, insulin receptor, AKT, ERK, mTOR, and S6 kinase pathway activation by immunohistochemistry (IHC) and banked for future correlative studies. Blood and bone marrow samples, from patients with Ewing sarcoma, may be collected at baseline and periodically during treatment for minimal residual disease analysis by flow cytometry.
After completion of study treatment, patients are followed up periodically for 5 years.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (cixutumumab, temsirolimus)
Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.
Cixutumumab
Given IV
Laboratory Biomarker Analysis
Correlative studies
Temsirolimus
Given IV
Interventions
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Cixutumumab
Given IV
Laboratory Biomarker Analysis
Correlative studies
Temsirolimus
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Osteosarcoma
* Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)
* Rhabdomyosarcoma
* Non-rhabdomyosarcoma soft tissue sarcoma
* Patients must have had histologic verification of malignancy at original diagnosis or relapse
* All patients are required to submit archival tumor samples for immunohistochemical analysis (either paraffin-embedded tumor blocks or unstained slides)
* Tissue samples collected at original diagnosis or at relapse or at any subsequent resections or biopsies should be available and ready for shipment to the Biopathology Center (BPC) at time of study enrollment; the samples are required even if tissue samples have previously been sent to the BPC for other purposes or studies; blocks or slides should be shipped to the BPC within 7 days of study enrollment
* Patients must have radiographically measurable disease
* Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
* The following do not qualify as measurable disease:
* Malignant fluid collections (e.g., ascites, pleural effusions)
* Bone marrow infiltration
* Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or positron emission tomography \[PET\] scans)
* Elevated tumor markers in plasma or cerebrospinal fluid(CSF)
* Previously radiated lesions that have not demonstrated clear progression post radiation
* Leptomeningeal lesions that do not meet the measurements noted above
* Patient?s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months
* Patients must have a Lansky or Karnofsky performance status score of ? 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients ? 16 years of age
* Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* For patients with solid tumors without bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) ? 1,000/?L
* Platelet count ? 100,000/?L (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
* Hemoglobin ? 8.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* For patients with solid tumors and known bone marrow metastatic disease:
* ANC ? 750/?L
* Platelet count ? 50,000/?L (may receive platelet transfusions)
* Hemoglobin ? 8.0 g/dL (may receive RBC transfusions)
* For patients with known bone marrow metastatic disease, transfusions are permitted to meet both platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
* Creatinine clearance or radioisotope GFR ? 70 mL/min OR a serum creatinine based on age/gender as follows:
* 0.6 mg/dL (1 to \< 2 years of age)
* 0.8 mg/dL (2 to \< 6 years of age)
* 1.0 mg/dL (6 to \< 10 years of age)
* 1.2 mg/dL (10 to \< 13 years of age)
* 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to \< 16 years of age)
* 1.7 mg/dL (males) or 1.4 mg/dL (females) ( ? 16 years of age)
* Total bilirubin ? 1.5 times upper limit of normal (ULN)
* Serum glutamic pyruvate transaminase(SGPT) (alanine aminotransaminase \[ALT\]) ? 2.5 times ULN (for the purpose of this study, the ULN for SGPT is 45 U/L)
* Serum albumin ? 2 g/dL
* Patients with seizure disorder may be enrolled if receiving non-enzyme-inducing anticonvulsants and well controlled
* Patients with known type I or type II diabetes mellitus are not eligible
* Serum glucose values must be within the normal limits for age; if the initial blood glucose is a random sample that is outside normal limits, then a follow-up fasting blood glucose should be obtained and must be within the normal limits for age
* Serum cholesterol levels must be \< grade 2 (\< 300 mg/dL), and serum triglyceride levels must be \< grade 2 (\< 2.5 times ULN)
* Patients who are pregnant or breast-feeding are not eligible for this study
* Negative pregnancy tests must be obtained in girls who are post-menarchal
* Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of the study and for 3 months after the last dose of cixutumumab
* Patients who have an uncontrolled infection are not eligible
* Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible
* See Disease Characteristics
* There is no limit to the number of prior treatment regimens; however, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
* Patients must not have received myelosuppressive chemotherapy within 3 weeks of enrollment (6 weeks if prior nitrosourea)
* At least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim
* At least 7 days must have elapsed since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
* At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
* ? 2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); 3 months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if therapeutic doses of metaiodobenzylguanidine(MIBG) or other substantial bone marrow irradiation was given
* No evidence of active graft-vs-host disease and 2 months must have elapsed since stem cell transplant or rescue
* Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if Neulasta?)
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy, are not eligible
* Patients receiving insulin or growth hormone therapy are not eligible
* Patients who are receiving enzyme-inducing anticonvulsants are not eligible
* Use of warfarin is not allowed while on study; patients already on warfarin should use alternative anticoagulants while on this study; warfarin must not have been administered within 7 days of starting protocol therapy
* Patients who have received prior therapy targeting IGF-1R with either monoclonal antibodies or small molecule tyrosine kinase inhibitors are NOT eligible
* Prior treatment with mTOR inhibitors (e.g., rapamycin, temsirolimus, everolimus, deforolimus) is NOT allowed
* Patients who have had major surgery within 3 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter or limited tumor biopsy are not considered major surgery
1 Year
30 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Lars Wagner
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital and Research Center at Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Yale University
New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lee Memorial Health System
Fort Myers, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
Nicklaus Children's Hospital
Miami, Florida, United States
Florida Hospital Orlando
Orlando, Florida, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Memorial University Medical Center
Savannah, Georgia, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
The Childrens Mercy Hospital
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Overlook Hospital
Summit, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Columbia University/Herbert Irving Cancer Center
New York, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Stony Brook University Medical Center
Stony Brook, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Mercy Children's Hospital
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Palmetto Health Richland
Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
Scott and White Memorial Hospital
Temple, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Marshfield Clinic
Marshfield, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Quebec
Québec, , Canada
Countries
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Other Identifiers
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NCI-2012-01971
Identifier Type: REGISTRY
Identifier Source: secondary_id
ADVL1221
Identifier Type: -
Identifier Source: secondary_id
COG-ADVL1221
Identifier Type: -
Identifier Source: secondary_id
CDR0000734871
Identifier Type: -
Identifier Source: secondary_id
ADVL1221
Identifier Type: OTHER
Identifier Source: secondary_id
ADVL1221
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2012-01971
Identifier Type: -
Identifier Source: org_study_id