Clinical Trials /

SARC023: Ganetespib and Sirolimus in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors)

NCT02008877

Description:

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.

Related Conditions:
  • Malignant Peripheral Nerve Sheath Tumor
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ganetespib</span> and Sirolimos in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors)

Title

  • Brief Title: Ganetespib and Sirolimos in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors)
  • 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
  • Clinical Trial IDs

    NCT ID: NCT02008877

    ORG ID: SARC023

    NCI ID: CDMRP-NF120087

    Trial Conditions

    Malignant Peripheral Nerve Sheath Tumors (MPNST)

    Sarcoma

    Trial Interventions

    Drug Synonyms Arms
    ganetespib STA-9090 ganetespib / sirolimus
    Sirolimus Rapamycin ganetespib / sirolimus

    Trial Purpose

    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.

    Detailed 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 Arms

    Name Type Description Interventions
    ganetespib / sirolimus Experimental 28-day cycles of ganetespib + sirolimus ganetespib, Sirolimus

    Eligibility Criteria

    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

    Minimum Eligible Age: 16 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Grade the toxicity of ganetespib when administered in combination with sirolimus.

    Secondary Outcome Measures

    Clinical benefit of combined study drugs.

    Trial Keywords

    Malignant Peripheral Nerve Sheath Tumors

    MPNST

    Sarcoma

    Ganetespib

    Sirolimus

    mTOR inhibitor

    Heat shock protein

    Hsp90