Overview

This trial is active, not recruiting.

Conditions malignant peripheral nerve sheath tumors (mpnst), sarcoma
Treatments ganetespib, sirolimus
Phase phase 1/phase 2
Targets Hsp90, mTOR, BCR-ABL, EGFR, FKBP-12, KIT
Sponsor Sarcoma Alliance for Research through Collaboration
Collaborator Synta Pharmaceuticals Corp.
Start date December 2013
End date June 2017
Trial size 38 participants
Trial identifier NCT02008877, CDMRP-NF120087, SARC023

Summary

Phase 1: To assess the safety, tolerability, and maximum tolerated dose (MTD)/ recommended dose of ganetespib when administered in combination with sirolimus in patients with refractory or relapsed sarcomas including unresectable or metastatic sporadic or neurofibromatosis type 1 (NF1) associated MPNST. Phase I enrollment has been closed.

Phase 2: To determine the clinical benefit of ganetespib in combination with sirolimus for patients with unresectable or metastatic sporadic or NF1 associated MPNST.

United States Maryland
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
28-day cycles of ganetespib + sirolimus
ganetespib STA-9090
200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour
sirolimus Rapamycin
2mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.

Primary Outcomes

Measure
Grade the toxicity of ganetespib when administered in combination with sirolimus.
time frame: Toxicities will be evaluated each 28 day cycle for up to 1 year (13 cycles).

Secondary Outcomes

Measure
Clinical benefit of combined study drugs.
time frame: 4 months

Eligibility Criteria

Male or female participants at least 16 years old.

Inclusion Criteria: - Patients ≥ 16 years old - Patients with unresectable or metastatic histologically confirmed sporadic or NF1 associated high grade MPNST - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Patients must have at least 1 measurable tumor - Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy (toxicity < grade 2) - Must be able to swallow whole pills - Adequate organ function - Normal fasting cholesterol and triglycerides - May be on cholesterol medications Exclusion Criteria: - Patients receiving current treatment with corticosteroids or another immunosuppressive. Topical or inhaled corticosteroids are allowed. - Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases - Symptomatic congestive heart failure - Severely impaired lung function - Significant vascular disease - Uncontrolled diabetes - Active (acute or chronic) or uncontrolled severe infections hepatitis - Impairment of gastrointestinal function - Patients with an active, bleeding diathesis or significant coagulopathy - Use of cytochrome P450 isoenzyme 3A4 (CYP3A4)/ CYP2C19 substrates

Additional Information

Official title A Phase I/II Trial of Ganetespib in Combination With the mTOR Inhibitor Sirolimus for Patients With Recurrent or Refractory Sarcomas Including Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors
Principal investigator AeRang Kim, MD, PhD
Description Previously, no targeted agents have been able to cause tumor regression in a genetically engineered MPNST mouse model or human MPNST. Recently published data from Dr. Cichowski's laboratory demonstrated using Hsp90 inhibitors to enhance endoplasmic reticulum stress coupled with the mammalian target of rapamycin (mTOR) inhibitor sirolimus led to dramatic tumor shrinkage in a transgenic MPNST mouse model, which correlated with profound damage to the endoplasmic reticulum and cell death. Ganetespib is a novel, injectable, small molecule inhibitor of Hsp90 and is currently being investigated in adults with a broad range of tumor types with a favorable safety profile and promising early results. Ganetespib has been studied in preclinical in vivo models with a variety of targeted agents with no marked apparent pharmacological interactions. Sirolimus is a commercially available orally administered mTOR inhibitor and is the active metabolite of temsirolimus, which is FDA approved agent for advanced metastatic renal cell carcinoma. Sirolimus has been studied and tolerated in combination with multiple cytotoxic and targeted agents in a variety of tumor types. Based on strong preclinical rationale, the investigators hypothesize that ganetespib in combination with sirolimus will cause tumor regression in patients with refractory MPNSTs. The investigators propose a multi-institutional open label phase I/II trial of ganetespib in combination with sirolimus in patients with refractory sarcoma including MPNST. Hsp90 inhibitors and mTOR inhibitors have also both demonstrated benefit in a variety of preclinical bone and soft tissue sarcoma models. The investigators hypothesize that these agents that work on separate and potentially synergistic pathways will also be beneficial for other refractory bone and soft tissue sarcomas. Thus, the phase I component will be open to patients with refractory sarcomas, which will also expedite enrollment. Upon determination of the recommended dosing, a phase II study will be conducted. The phase II study population will be limited to patients with a diagnosis of MPNST.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Sarcoma Alliance for Research through Collaboration.