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

NCT02008877 | Completed Phase 1 Results DMC

• 2 other identifiers: SARC023CDMRP-NF120087
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Malignant Peripheral Nerve Sheath Tumors (MPNST); Sarcoma

Keywords

Malignant Peripheral Nerve Sheath Tumors; MPNST; Sarcoma; Ganetespib; Sirolimus; mTOR inhibitor; Heat shock protein; Hsp90

Outcome Measures

Primary Outcomes (2)

• Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus.

  To assess the safety, tolerability, and maximum tolerated/ recommended dose of ganetespib when administered in combination with sirolimus in patients with refractory sarcomas or unresectable or metastatic sporadic or neurofibromatosis type 1 (NF1) associated MPNST. Toxicities observed during the first cycle will be used to define the MTD/Recommended dose. Toxicity will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DLT will be defined as any of the following events that are possibly, probably, or definitely attributable to ganetespib or sirolimus. The DLT observation period for the purposes of dose escalation will be the first cycle of therapy.

  Toxicities will be evaluated over the first treatment cycle (each cycle=28 days)

• Clinical Benefit of Ganetespib in Combination With Sirolimus

  Assessed using the World Health Organization (WHO) criteria. Tumor assessments will be obtained every 2 cycles. Clinical benefit is defined as stable disease, Partial Response (PR), Complete Response (CR). For patients who experience progression by WHO but in the opinion of the treating investigator are deriving benefit from therapy and have not otherwise met off treatment or off study criteria, may continue on treatment as long as patient has not met progression by RECIST 1.1.

  Response evaluations will be performed after every 2 treatment cycles (each cycle=28 days)

Secondary Outcomes (6)

• Change in Plasma Pharmacokinetic Profile of Ganetespib and Sirolimus When Administered in Combination-Observed Maximum Plasma Concentration (Cmax)

  Pre-therapy levels drawn at baseline and pharmacokinetic analysis occurs on Cycle 1 Day 15

• Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells

  Baseline and Cycle 1 Day 15

• Patient-reported Pain Severity and the Impact of Pain on Daily Activities

  Baseline and prior to Cycle 3

• Utility of Three-dimensional MRI (3D-MRI) Analysis in Comparison to 1-dimensional and 2-dimensional Measurements

  4 months

• Plasma Pharmacokinetic Profile of Ganetespib When Administered in Combination With Sirolimus

  Cycle 1 Day 15

Study Arms (1)

ganetespib / sirolimus

EXPERIMENTAL

28-day cycles of ganetespib + sirolimus

Drug: ganetespib; Drug: Sirolimus

Interventions

ganetespib DRUG

Phase 1 Dose 1: 150 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour; Phase 1 Dose 2: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour; Phase 2: 200 mg/m² IV on days 1, 8, and 15 intravenously over 1 hour

Also known as: STA-9090

ganetespib / sirolimus

Sirolimus DRUG

4mg taken orally once daily on a continuous dosing schedule; Loading dose 12 mg on cycle 1 day 1 only.

Also known as: Rapamycin

ganetespib / sirolimus

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• Synta Pharmaceuticals Corp.: collaborator
• United States Department of Defense: collaborator

Study Sites (7)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Kim A, Lu Y, Okuno SH, Reinke D, Maertens O, Perentesis J, Basu M, Wolters PL, De Raedt T, Chawla S, Chugh R, Van Tine BA, O'Sullivan G, Chen A, Cichowski K, Widemann BC. Targeting Refractory Sarcomas and Malignant Peripheral Nerve Sheath Tumors in a Phase I/II Study of Sirolimus in Combination with Ganetespib (SARC023). Sarcoma. 2020 Jan 30;2020:5784876. doi: 10.1155/2020/5784876. eCollection 2020.

  PMID: 32089640 DERIVED

Related Links

• SARC Website

MeSH Terms

Conditions

Neurofibrosarcoma; Sarcoma

Interventions

STA 9090; Sirolimus

Condition Hierarchy (Ancestors)

Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: SARC
• Organization: SARC

sarc@sarctrials.org

(734) 930-7600

Study Officials

• AeRang Kim, MD, PhD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

• Brigitte Widemann, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 11, 2013
• Study Start: December 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: July 1, 2018
• Last Updated: May 15, 2019
• Results First Posted: May 2, 2019

Record last verified: 2019-04

Locations

US (7)