Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients With Solid Tumors
The purpose of this study is to determine the safest and most effective oral dose combinations of sorafenib and irinotecan in pediatric patients with solid tumors, i.e. relapsed or refractory.
Rhabdomyosarcoma and Other Soft Tissue Sarcomas
Ewing's Sarcoma Family of Tumors
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients With Relapsed or Refractory Solid Tumors|
- Toxicity Profile [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]Determine the toxicity profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of sorafenib, when administered in combination with oral irinotecan in children with relapsed or refractory solid tumors.
- Patient Related Outcomes [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Demonstrate the feasibility of incorporating measurement of patient-related outcome into a four site phase 1 trial of sorafenib and irinotecan for children and adolescents.
Demonstrate feasibility: defined as 70% of participants will complete the 5 patient-reported outcomes (PROs) (pain, fatigue, worry, sadness and physical functioning) at both baseline (pre-treatment) and at the end of the first course and missing data will not be greater than 15% across the 5 PROs at either data point.
- Pharmacokinetic Profile [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]Describe the plasma pharmacokinetic profile of sorafenib and irinotecan when administered as combination therapy in children and adolescents.
- Disease Evaluation [ Time Frame: 24 months ] [ Designated as safety issue: No ]Evaluate disease response, based on criteria for measurable lesions (RECIST) and evaluable lesions, to guide further development in phase 2 studies.
- Integration of Patient Related Outcomes with other outcome measures [ Time Frame: 24 months ] [ Designated as safety issue: No ]Correlate and integrate the PRO scores with traditional endpoints of toxicity, pharmacokinetic profile, and tumor response associated with the sorafenib and irinotecan combination.
|Study Start Date:||December 2011|
|Study Completion Date:||January 2015|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Combination Therapy
Three to 6 patient will be enrolled at each dose level and dose escalations will proceed in the absence of dose-limiting toxicity attributed to therapy, first with dose escalation of sorafenib and then, if tolerated, escalation of irinotecan.
sorafenib (50 and 200 mg tablets) orally twice daily, on a continuous schedule at a starting dose of 150mg/m2/dose.Drug: irinotecan
irinotecan (70 mg/m2/dose) orally, concurrently, once daily,starting at the beginning of the 21 day cycle,repeated every 21 days
Sorafenib, a multi-kinase inhibitor of several targets felt to be important in tumor growth and angiogenesis, has been well studied and shown promising clinical results in adult cancer patients and the Maximum Tolerated Dose or MTD has been determined in pediatric patients. Irinotecan is known to be effective and is widely used in pediatric malignancies. The combination of sorafenib with irinotecan is of interest as these agents have different mechanisms of action. In addition, the combination has been evaluated in adult patients and deemed tolerable without alterations in the pharmacokinetic (PK) profile at the MTD. The trial we are proposing also offers the advantage of being a completely oral regimen, adding convenience and cost effectiveness. Given these considerations, if the sorafenib/irinotecan combination proves tolerable in phase I studies and shows efficacy in phase II studies, it would be an attractive combination to incorporate into existing chemotherapy regimens for pediatric cancer.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01518413
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Maryland|
|National Cancer Institute|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Children's Hospital Boston/Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Holly Meany, MD||Children's Research Institute|