Phase 1 Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients With Relapsed or Refractory Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- sorafenib
- Conditions
- Rhabdomyosarcoma and Other Soft Tissue Sarcomas
- Sponsor
- HMeany
- Enrollment
- 17
- Locations
- 4
- Primary Endpoint
- Patient Related Outcomes
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
HMeany
Holly Meany, MD
Children's National Research Institute
Eligibility Criteria
Inclusion Criteria
- •AGE: \>=2 year and \<22 years of age.
- •DIAGNOSIS: solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors and brain tumors.
- •MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable disease.
- •THERAPEUTIC OPTIONS:
- •The patient's cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities.
- •PRIOR THERAPY:
- •Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrolling on this study.
- •No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study enrollment.
- •Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry.
- •Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.
Exclusion Criteria
- •Clinically significant unrelated systemic illness, such as serious infections, hepatic,renal or other organ dysfunction, which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate the agents used in this trial or are likely to interfere with the study procedures or results.
- •Patients with known intra-axial metastatic central nervous system lesions.
- •Pregnant or breast-feeding females are excluded because of the potential harmful effects of sorafenib and irinotecan on a developing fetus or nursing child.
- •Patients currently receiving other anticancer agents or radiation therapy.
- •Patients currently receiving other investigational agents.
- •Prior treatment with a sorafenib containing regimen.
- •Inability to swallow pills.
- •Evidence of bleeding diathesis and/or on therapeutic anti-coagulation medications.
- •Patients with known Gilbert syndrome.
- •Patients who take cytochrome P450 enzyme-inducing antiepileptic agents (phenytoin, carbamazepine, phenobarbitol), rifampin, erythromycin, azithromycin, azole antifungals, grape fruit juice or St. Johns Wort. Patients must have discontinued these medications at least 7 days prior to enrollment of trial.
Arms & Interventions
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.
Intervention: sorafenib
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.
Intervention: irinotecan
Outcomes
Primary Outcomes
Patient Related Outcomes
Time Frame: 24 months
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.
Toxicity Profile
Time Frame: 24 months
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.
Secondary Outcomes
- Disease Evaluation(24 months)
- Integration of Patient Related Outcomes with other outcome measures(24 months)
- Pharmacokinetic Profile(24 months)