Phase 2
N=20
SARC023: Ganetespib and Sirolimus in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors)
Malignant Peripheral Nerve Sheath Tumors (MPNST) · Sarcoma
Bottom Line
View on ClinicalTrials.gov: NCT02008877 ↗Enrolled (actual)
20
Serious AEs
45.0%
Results posted
May 2019
Primary outcome: Primary: Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus. — 0; 1 DLTs
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ganetespib (Drug); Sirolimus (Drug)
- Age
- Pediatric, Adult, Older Adult · 16+ yrs
- Sex
- All
- Sponsor
- Sarcoma Alliance for Research through Collaboration
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus. |
0; 1 | — |
| PRIMARY Clinical Benefit of Ganetespib in Combination With Sirolimus |
1; 0 | — |
| SECONDARY Change in Plasma Pharmacokinetic Profile of Ganetespib and Sirolimus When Administered in Combination-Observed Maximum Plasma Concentration (Cmax) |
12.1; 12.5 | — |
| SECONDARY Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells |
0.81; 0.84; 1.20; 1.44; 1.25; 0.54 | — |
| SECONDARY Patient-reported Pain Severity and the Impact of Pain on Daily Activities |
7.5; 7.5; 6.49; 5; 4.75; 3.14 | — |
| SECONDARY Utility of Three-dimensional MRI (3D-MRI) Analysis in Comparison to 1-dimensional and 2-dimensional Measurements |
— | — |
| SECONDARY Plasma Pharmacokinetic Profile of Ganetespib When Administered in Combination With Sirolimus |
6.4; 6.0 | — |
| SECONDARY Determine Maximum Tolerated Dose (MTD)/Recommended Dose (RD) of Ganetespib |
3; 6; 10 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT02008877). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.