Cixutumumab and Temsirolimus in Treating Younger Patients With Solid Tumors That Have Recurred or Not Responded to Treatment
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|ClinicalTrials.gov Identifier: NCT00880282|
Recruitment Status : Completed
First Posted : April 13, 2009
Last Update Posted : April 29, 2014
|Condition or disease||Intervention/treatment||Phase|
|Unspecified Childhood Solid Tumor, Protocol Specific||Biological: cixutumumab Drug: temsirolimus Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
I. To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of IMC-A12 (anti-insulin growth factor-1 receptor monoclonal antibody) (cixutumumab) administered as an intravenous infusion once weekly in combination with CCI-779 (temsirolimus) administered intravenously once weekly to children with refractory solid tumors.
II. To define and describe the toxicities of IMC-A12 in combination with temsirolimus administered on this schedule.
III. To characterize the pharmacokinetics of IMC-A12 in combination with temsirolimus in children with refractory cancer.
I. To preliminarily define the antitumor activity of the combination of IMC-A12 and temsirolimus within the confines of a Phase I study.
II. To assess the biologic activity of IMC-A12 by assessing: changes in insulin-like growth factor receptor (IGFR) expression and phosphorylation and insulin-receptor expression and phosphorylation in peripheral blood mononuclear cells (PBMNC).
III. To assess the biological activity of temsirolimus by measuring levels of phosphorylated (phosphor)-ribosomal protein S6 kinase, 70kDa, polypeptide 1 (S6K1), phosphor-protein kinase B (AKT), phosphor-eukaryotic translation initiation factor 4 gamma, 1 (eIF4G) in PBMNC.
IV. To assess the incidence of IGFR expression as well as mechanistic target of rapamycin (mTOR) pathway activation in recurrent or refractory solid tumors of childhood.
Patients receive cixutumumab intravenously (IV) over 60 minutes 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.
After completion of study therapy, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of IMC-A12 (Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody) in Combination With CCI-779 (Temsirolimus) in Pediatric Patients With Recurrent or Refractory Solid Tumors|
|Study Start Date :||April 2009|
|Actual Primary Completion Date :||October 2012|
Experimental: Treatment (cixutumumab, temsirolimus)
Patients receive cixutumumab IV over 60 minutes 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.
Other: pharmacological study
Other Name: pharmacological studies
Other: laboratory biomarker analysis
- Maximum-tolerated dose and recommended phase II dose based on the incidence of dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ]
- Toxicities as assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after the last dose of treatment ]
- Pharmacokinetics (PK) of cixutumumab [ Time Frame: At end of infusion, at 1, 3, 6, and 24 hours, days 1, 4, 8, 15, 22, and 28 (of course 1), and days 15 and 28 (of course 2) ]The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Pharmacokinetics of temsirolimus [ Time Frame: At end of infusion, at 15 and 30 minutes, at 1, 3, 6, and 24 hours, days 1, 4, 7, and 28 (of course 1), and days 15 and 28 (course 2) ]The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Disease response according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 4 years ]Reported descriptively.
- Change IGFR and insulin receptor expression [ Time Frame: From baseline to up to 28 days (of course 1) ]Summary statistics and descriptive plots will be generated for IGFR expression. The changes will be assessed using paired t-test or Wilcoxon matched pairs signed rank sum test when appropriate.
- Change in levels of S6K1, AKT, eIF4G, and associated phosphoproteins [ Time Frame: From baseline to up to 28 days (of course 1) ]Summary statistics and descriptive plots will be generated. The changes will be assessed using paired t-test or Wilcoxon matched pairs signed rank sum test when appropriate.
- Incidence of IGFR expression as well as mTOR pathway activation [ Time Frame: At baseline ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00880282
Hide Study Locations
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|Childrens Hospital of Orange County|
|Orange, California, United States, 92868-3874|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Illinois|
|Lurie Children's Hospital-Chicago|
|Chicago, Illinois, United States, 60614|
|United States, Indiana|
|Indiana University Medical Center|
|Indianapolis, Indiana, United States, 46202|
|Riley Hospital for Children|
|Indianapolis, Indiana, United States, 46202|
|United States, Maryland|
|Mark O Hatfield-Warren Grant Magnuson Clinical Center|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|C S Mott Children's Hospital|
|Ann Arbor, Michigan, United States, 48109|
|United States, Minnesota|
|University of Minnesota Medical Center-Fairview|
|Minneapolis, Minnesota, United States, 55455|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Oregon|
|Oregon Health and Science University|
|Portland, Oregon, United States, 97239|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|University of Texas Southwestern Medical Center|
|Dallas, Texas, United States, 75390|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|United States, Wisconsin|
|Midwest Children's Cancer Center|
|Milwaukee, Wisconsin, United States, 53226|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Centre Hospitalier Universitaire Sainte-Justine|
|Montreal, Quebec, Canada, H3T 1C5|
|Principal Investigator:||Maryam Fouladi||Children's Oncology Group|