NCT01182883WithdrawnPhase 1
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
Conditions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Primary Endpoint
- To determine the MTD and recommended Phase II dose of IMC-A12 (anti-IGFR monoclonal antibody) IV once weekly in combination with temsirolimus IV weekly to children with refractory solid tumors.
Study Overview
Brief Summary
Background:
- IMC-A12 is an experimental substance designed to inhibit a protein called Type I Insulin-Like Growth Factor Receptor (IGF-1R), which can be found on cancer cells and can promote cancer growth. Temsirolimus is a drug that the U.S. Food and Drug Administration has approved to treat advanced renal cell carcinoma in adults. Researchers do not know if the combination of IMC-A12 and temsirolimus will work in children, but want to determine whether these two drugs may be an effective treatment for recurrent tumors.
Objectives:
- To determine the safety and effectiveness of IMC-A12 and temsirolimus in treating children and adolescents with solid tumors.
- To determine possible side effects of the combination of IMC-A12 and temsirolimus.
Eligibility:
- Children and adolescents between 12 months and 21 years of age who have solid tumors that have not responded to or have relapsed after standard treatment.
Design:
- Participants will be screened with a medical history, physical examination, and imaging studies.
- Participants will receive IMC-A12 and temsirolimus in 28-day cycles of treatment. IMC-A12 will be given as an infusion over 1 hour, once a week, for 4 weeks. Temsirolimus will also be given after IMC-A12 over 30 minutes, once a week, for 4 weeks.
- Participants may continue to receive IMC-A12 and temsirolimus for up to 2 years unless serious side effects develop or the treatment stops being effective.
- Participants will have additional physical exams, blood and urine tests, and imaging studies regularly during each treatment cycle.
- Participants will be followed at regular intervals after the end of the study to collect tumor response and progression data....
Detailed Description
Background
- IMC-A12 is a fully recombinant IgG1monoclonal antibody to the insulin-like growth factor receptor (IGFR). It acts as an antagonist of IGF-1 and IGF-2 ligand binding and blocks ligand binding to IGF-1R and inhibits downstream signaling of the two major insulin-like growth factor pathways: MAPK and PI3K/AKT.
- Temsirolimus is a small molecule inhibitor of mTOR, which like rapamycin and everolimus forms a complex with FK506-binding protein (FKBP)12 and mTOR, inhibiting mTOR and leading to anti-proliferative effects, including G1 phase cell cycle arrest and apoptosis.
- Inhibition of mTOR signaling leads to upregulation of IGF-1R signaling which leads to activation of the PI3K/AKT/mTOR pathway. Pediatric pre-clinical models have demonstrated synergistic anti-tumor effects combining IGF-1R antibodies and mTOR inhibitors.
Objectives
- To determine the maximum tolerated dose (MTD) and recommended Phase II dose of IMC-A12 (anti-insulin growth factor-1 receptor monoclonal antibody) administered as an intravenous infusion once weekly in combination with temsirolimus administered intravenously once weekly to children with refractory solid tumors.
- To define the toxicities of the combination regimen and characterize the pharmacokinetics of IMC-A12 in combination with temsirolimus in this patient population.
- Secondary objectives include defining in a preliminary fashion antitumor activity, assessing biologic activity of IMC-A12 and temsirolimus and assessing the incidence of IGFR expression and mTOR pathway activation in recurrent or refractory solid tumors of childhood.
Eligibility
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 21 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Eligibility
- •Patients > 12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with intrinsic brain stem tumors, optic pathway gliomas or pineal tumors and elevations of serum or CSF alpha-fetoprotein or beta-HCG) of measureable or evaluable relapsed or refractory solid tumors. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival.
- •Must have fully recovered from acute toxic effects from all prior therapy, which has been completed within the specified prior time frame.
- •Have adequate organ function as determined by laboratory evaluation including normal random or fasting blood glucose within the upper normal limits for age and grade < 2 serum cholesterol and triglyceride levels.
- •Subjects with uncontrolled infection, known type I or type II diabetes mellitus, known bone marrow involvement or who have received prior monoclonal antibody therapy targeting IGF-1R or temsirolimus are not eligible.
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
To determine the MTD and recommended Phase II dose of IMC-A12 (anti-IGFR monoclonal antibody) IV once weekly in combination with temsirolimus IV weekly to children with refractory solid tumors.
To define toxicities and characterize pharmacokinetics.
Secondary Outcomes
- Define in a preliminary fashion antitumor activity, assess biologic activity of IMC-A12 and temsirolimus and assess the incidence of IGFR expression and mTOR pathway activation in recurrent or refractory solid tumors of childhood.
Investigators
Similar Trials
Completed
Phase 1
Cixutumumab and Temsirolimus in Treating Younger Patients With Solid Tumors That Have Recurred or Not Responded to TreatmentUnspecified Childhood Solid Tumor, Protocol SpecificNCT00880282National Cancer Institute (NCI)39
Completed
Phase 1
A Study of IMC-A12 Every 2 Weeks in Patients With Tumors Who No Longer Respond to Treatment or No Treatment is AvailableAdvanced Solid TumorsNCT00785941Eli Lilly and Company16
Completed
Phase 1
A Study of IMC-A12 in Participants With Tumors Who No Longer Respond to Treatment or For Whom No Treatment is AvailableAdvanced Solid TumorsNCT00785538Eli Lilly and Company24
Completed
Phase 1
IMC-A12 in Treating Young Patients With Relapsed or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor or Other Solid TumorUnspecified Childhood Solid Tumor, Protocol SpecificRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal TumorNCT00609141National Cancer Institute (NCI)34
Completed
Phase 2
Cixutumumab in Treating Patients With Relapsed or Refractory Solid TumorsAdult RhabdomyosarcomaAdult Synovial SarcomaRecurrent Adrenocortical CarcinomaRecurrent Childhood RhabdomyosarcomaRecurrent Adult Soft Tissue SarcomaRecurrent RetinoblastomaRecurrent Childhood Liver CancerRecurrent OsteosarcomaChildhood HepatoblastomaChildhood Synovial SarcomaPreviously Treated Childhood RhabdomyosarcomaRecurrent Childhood Soft Tissue SarcomaRecurrent Ewing Sarcoma/Peripheral PrimitiveNeuroectodermal TumorRecurrent NeuroblastomaRecurrent Wilms Tumor and Other Childhood Kidney TumorsNCT00831844National Cancer Institute (NCI)116