Rhabdomyosarcoma Clinical Trial
Official title:
A Phase II Study of Cixutumumab (IMC-A12) in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors
Verified date | November 2018 |
Source | National Cancer Institute (NCI) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This phase II trial studies how well cixutumumab and temsirolimus work in treating patients with recurrent or refractory sarcoma. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab and temsirolimus together may kill more tumor cells.
Status | Completed |
Enrollment | 46 |
Est. completion date | April 1, 2014 |
Est. primary completion date | April 1, 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Year to 30 Years |
Eligibility |
Inclusion Criteria: - Patients with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, are eligible: - 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 |
Country | Name | City | State |
---|---|---|---|
Canada | Centre Hospitalier Universitaire Sainte-Justine | Montreal | Quebec |
Canada | Centre Hospitalier Universitaire de Quebec | Quebec | |
United States | Children's Hospital Medical Center of Akron | Akron | Ohio |
United States | University of New Mexico Cancer Center | Albuquerque | New Mexico |
United States | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia |
United States | Sinai Hospital of Baltimore | Baltimore | Maryland |
United States | Children's Hospital of Alabama | Birmingham | Alabama |
United States | University of Alabama at Birmingham Cancer Center | Birmingham | Alabama |
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Massachusetts General Hospital Cancer Center | Boston | Massachusetts |
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 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois |
United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
United States | Palmetto Health Richland | Columbia | South Carolina |
United States | Nationwide Children's Hospital | Columbus | Ohio |
United States | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas |
United States | Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center | Denver | Colorado |
United States | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan |
United States | Lee Memorial Health System | Fort Myers | Florida |
United States | Cook Children's Medical Center | Fort Worth | Texas |
United States | BI-LO Charities Children's Cancer Center | Greenville | South Carolina |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | Connecticut Children's Medical Center | Hartford | Connecticut |
United States | University of Hawaii Cancer Center | Honolulu | Hawaii |
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 | Riley Hospital for Children | Indianapolis | Indiana |
United States | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana |
United States | University of Mississippi Medical Center | Jackson | Mississippi |
United States | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida |
United States | The Childrens Mercy Hospital | Kansas City | Missouri |
United States | East Tennessee Childrens Hospital | Knoxville | Tennessee |
United States | University of Kentucky/Markey Cancer Center | Lexington | Kentucky |
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 | Marshfield Clinic | Marshfield | Wisconsin |
United States | Nicklaus Children's Hospital | Miami | Florida |
United States | Children's Hospital of Wisconsin | Milwaukee | Wisconsin |
United States | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota |
United States | Morristown Medical Center | Morristown | New Jersey |
United States | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee |
United States | Yale University | New Haven | Connecticut |
United States | Ochsner Medical Center Jefferson | New Orleans | Louisiana |
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 | Children's Hospital and Research Center at Oakland | Oakland | California |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
United States | Children's Hospital and Medical Center of Omaha | Omaha | Nebraska |
United States | Children's Hospital of Orange County | Orange | California |
United States | Florida Hospital Orlando | Orlando | Florida |
United States | Nemours Children's Clinic - Orlando | Orlando | Florida |
United States | Lucile Packard Children's Hospital Stanford University | Palo Alto | California |
United States | Nemours Children's Clinic - Pensacola | Pensacola | Florida |
United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Legacy Emanuel Children's Hospital | Portland | Oregon |
United States | Oregon Health and Science University | Portland | Oregon |
United States | Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia |
United States | Mayo Clinic | Rochester | Minnesota |
United States | Mercy Hospital Saint Louis | Saint Louis | Missouri |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida |
United States | UCSF Medical Center-Parnassus | San Francisco | California |
United States | Memorial University Medical Center | Savannah | Georgia |
United States | Seattle Children's Hospital | Seattle | Washington |
United States | Providence Sacred Heart Medical Center and Children's Hospital | Spokane | Washington |
United States | Stony Brook University Medical Center | Stony Brook | New York |
United States | Overlook Hospital | Summit | New Jersey |
United States | Mary Bridge Children's Hospital and Health Center | Tacoma | Washington |
United States | Scott and White Memorial Hospital | Temple | Texas |
United States | Mercy Children's Hospital | Toledo | Ohio |
United States | Children's National Medical Center | Washington | District of Columbia |
United States | Alfred I duPont Hospital for Children | Wilmington | Delaware |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States, Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Objective Response Rate (PR or CR) by Response Evaluation Criteria in Solid Tumors (RECIST). | Per Response evaluation criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR)= CR+PR. The combination of sufficient activity is considered if the true response rate is 35% or greater. | 6 cycles (168 days) | |
Primary | Number of Cycles of Toxicity | The number of patients-cycles where CTC Version 4 grade 3 or higher increased Alanine aminotransferase was observed | Duration of protocol therapy - Up to 25 cycles (700 days) | |
Secondary | Progression-free Interval | Percentage Probability of remaining progression-free 5 years after enrollment estimated by the method of Kaplan and Meier | 10 months after enrollment | |
Secondary | Expression Levels of IGF-1R, Insulin Receptor, ERK, RON, and mTOR | Number of patients expressing insulin-like growth factor 1 receptor (IGF-1R), insulin receptor, ERK, RON, and mammalian target of rapamycin (mTOR) at levels 0, 1+, 2+, 3+ by immunohistochemistry. | Baseline | |
Secondary | Number of Patients With Detectable Bone Marrow Micrometastatic Disease Estimated as the Proportion of Eligible Patients Entered Into the Ewing Sarcoma Stratum Who Have Detectable Tumor Cells in the Marrow at Enrollment | Baseline |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04388839 -
Evolutionary Therapy for Rhabdomyosarcoma
|
Phase 2 | |
Withdrawn |
NCT04906876 -
A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas
|
Phase 2 | |
Completed |
NCT01674101 -
Effects of Preoperative Physical Therapy in Patients With Lower Extremity Malignancy
|
N/A | |
Completed |
NCT00520936 -
A Study of Pemetrexed in Children With Recurrent Cancer
|
Phase 2 | |
Completed |
NCT03655587 -
Impact of an Orthotic Intervention in Children With Peripheral Neuropathy
|
N/A | |
Recruiting |
NCT06094101 -
Personalized Vaccination in Fusion+ Sarcoma Patients (PerVision)
|
Phase 1/Phase 2 | |
Recruiting |
NCT04625907 -
FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04095221 -
A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma
|
Phase 1/Phase 2 | |
Completed |
NCT01661400 -
Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04337177 -
Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT02945800 -
Nab-Paclitaxel and Gemcitabine for Recurrent/Refractory Sarcoma
|
Phase 2 | |
Not yet recruiting |
NCT06029465 -
Analyzing Engagement Trends in Rhabdomyosarcoma Clinical Trials
|
||
Terminated |
NCT02536183 -
A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT00592592 -
Proton RT for the Treatment of Pediatric Rhabdomyosarcoma
|
Phase 2 | |
Completed |
NCT00187174 -
Everolimus for Treating Pediatric Patients With Recurrent or Refractory Tumors
|
Phase 1 | |
Completed |
NCT01505569 -
Auto Transplant for High Risk or Relapsed Solid or CNS Tumors
|
N/A | |
Active, not recruiting |
NCT03220035 -
Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
Completed |
NCT05093322 -
A Study of Surufatinib in Combination With Gemcitabine in Pediatric, Adolescent, and Young Adult Patients With Recurrent or Refractory Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT04956198 -
Drug Sensitivity and Mutation Profiling
|
||
Recruiting |
NCT04791228 -
A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors
|
Phase 2 |