Clinical Trials Logo

Clinical Trial Summary

This is a Phase I study of the combination of three drugs: sirolimus, cyclophosphamide, and topotecan. This is the first study to evaluate the safety and clinical activity of the combination of oral sirolimus, oral cyclophosphamide and oral topotecan in pediatric and young adult patients with relapsed and refractory solid tumors.

In this phase I study, the mTOR inhibitor sirolimus will be administered in combination with oral cyclophosphamide and oral topotecan to children with relapsed or refractory solid tumors. The primary aim of this study is to recommend a phase II dose schedule and describe the toxicity of this combination. Myelosuppression will be a targeted toxicity.


Clinical Trial Description

The combination of cyclophosphamide and topotecan is well-tolerated and provides an oral therapy option for heavily pre-treated patients. The toxicity profile and activity level suggest that this combination will provide a useful platform onto which novel compounds may be added. Sirolimus has been shown to demonstrate single-agent activity in preclinical models of rhabdomyosarcoma, Ewing sarcoma, medulloblastoma, glioblastoma, neuroblastoma, and osteosarcoma. Sirolimus has also been shown to have additive effects in pre-clinical models of solid tumors when combined with cyclophosphamide. This trial therefore will evaluate the combination of sirolimus with cyclophosphamide and topotecan. Pharmacokinetic studies of sirolimus as well as pharmacodynamic studies to assess antiangiogensis and inhibition of the mTOR pathway will be done.

Patients will be accrued to dose levels in cohorts of 3 using a 3 + 3 design. Patients will initially be enrolled on dose level 1. Patients will receive daily oral sirolimus and cyclophosphamide on days 1 - 21 in a 28 day cycle. This will be combined with oral topotecan given on days 1 - 14. Sirolimus will be dosed based on steady-state plasma trough concentrations with a goal level in dose level 1 of 3-7.9 ng/ML and goal levels in subsequent dose levels of 8-12.0 ng/ML. Dosing of cyclophosphamide and topotecan will be 25 mg/m2/dose and 0.8 mg/ m2 /dose respectively for dose levels 1 and 2. Level 3 dosing will escalate cyclophosphamide to 50 mg/ m2/dose. If level 1 dosing is not tolerated, patients will then be enrolled in a level -1 cohort with cyclophosphamide and sirolimus administered only on days 1 - 14. If level -1 is not tolerated, patients will be enrolled in level -2 with topotecan administration limited to days 1 - 7. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01670175
Study type Interventional
Source University of California, San Francisco
Contact
Status Completed
Phase Phase 1
Start date August 2012
Completion date September 2016

See also
  Status Clinical Trial Phase
Terminated NCT01846429 - Oral Bicarbonate as Adjuvant for Pain Reduction in Patients With Tumor Related Pain Phase 1
Completed NCT01359982 - Safety and Pharmacokinetic Study of RRx-001 in Cancer Subjects Phase 1
Completed NCT01648764 - A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread Phase 1
Completed NCT00725634 - A Phase 1 Dose-Escalation Study in Advanced Solid Tumors, Lymphomas or Multiple Myeloma Phase 1
Recruiting NCT04083599 - GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors Phase 1/Phase 2
Recruiting NCT05141474 - Assessment of the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors Early Phase 1
Active, not recruiting NCT02999750 - EXtendedAnalysis for Cancer Treatment N/A
Completed NCT01457118 - An Extension Study of NKTR-102 in Cancer Patients Previously Enrolled in NKTR-102 Studies Phase 2
Active, not recruiting NCT05539157 - Study to Evaluate JCXH-211 as Monotherapy in Patients With Malignant Solid Tumors Phase 1
Recruiting NCT04571892 - A Clinical Study to Observe the Safety and Efficacy of ScTIL210 in the Treatment of Malignant Solid Tumors Phase 1/Phase 2
Recruiting NCT05468359 - Safety and Efficacy of Cyclophosphamide, Sorafenib, Bevacizumab, and Atezolizumab in Pediatric Solid Tumor Patients Phase 1/Phase 2
Recruiting NCT04168528 - Phase I/IIa Study of 68GaNOTA-Anti-MMR-VHH2 for PET/CT Phase 1/Phase 2
Recruiting NCT04145622 - Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors Phase 1/Phase 2
Recruiting NCT06057038 - A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors Phase 1
Completed NCT02844400 - Cancer Patients' Performance Status Assessed Using Cardiopulmonary Exercise Testing and Wearable Data Generation
Completed NCT00452413 - A Study of Enzastaurin and Erlotinib in Participants With Solid Tumors and Lung Cancer Phase 1/Phase 2
Completed NCT03553108 - A Study Using Olaparib Tablets for Subjects With Advanced Solid Tumours. Phase 1
Recruiting NCT06391775 - Trial to Assess the Safety and Preliminary Efficacy of GEN1055 on Malignant Solid Tumors as Monotherapy and as Combination Therapy Phase 1/Phase 2
Recruiting NCT04076137 - Targeted T-cell Therapy in Solid Tumors Early Phase 1
Terminated NCT03192345 - A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and Cemiplimab in Patients With Advanced Solid Tumors Phase 1