Trial · NCT02008877
SARC023: Ganetespib and Sirolimus in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors)
NCT02008877, Phase 1, Phase 2, Completed, Sarcoma Alliance for Research through Collaboration; results first posted 2019-05-02
3 sourcestrials-2026-11-12-0.4.0
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ConductScience Library. SARC023: Ganetespib and Sirolimus in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors). Trials, record NCT02008877. Release trials-2026-11-12-0.4.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02008877
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- SARC023: Ganetespib and Sirolimus in Patients With MPNST (Malignant Peripheral Nerve Sheath Tumors)
- NCT number
- NCT02008877
- Status
- Completed
- Phases
- Phase 1, Phase 2
- Enrollment
- 20 participants, actual
- Lead sponsor
- Sarcoma Alliance for Research through Collaboration
- Conditions
- Malignant Peripheral Nerve Sheath Tumors (MPNST), Sarcoma
- Interventions
- ganetespib, Sirolimus
- First posted
- 2013-12-11
- Last updated
- 2019-05-15
- Results first posted
- 2019-05-02
Source ClinicalTrials.gov
Registered outcomes8
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus. | Toxicities will be evaluated over the first treatment cycle (each cycle=28 days) | 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. |
| Primary | Clinical Benefit of Ganetespib in Combination With Sirolimus | Response evaluations will be performed after every 2 treatment cycles (each cycle=28 days) | 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. |
| Secondary | 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 | To describe the plasma pharmacokinetic profile of ganetespib and sirolimus when administered in combination therapy. |
| Secondary | Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells | Baseline and Cycle 1 Day 15 | To explore changes in pharmacodynamic parameters in peripheral blood mononuclear cells performed on day 1 prior to ganetespib and sirolimus administration, and on day 15, 6 hours post drug administration. Hsp inhibition (Hsp70), mTOR inhibition (phospho-S6 and Akt Phosphorylation), UPR activation (EIF2alpha phosphorylation) will be explored. Western blot analyses were performed for phospho (p)-Akt, p-eIF2α, p-S6, and Hsp70. The absorbance of each phosphoprotein lane was recorded and protein levels were determined after normalizing for levels of corresponding total protein. |
| Secondary | Patient-reported Pain Severity and the Impact of Pain on Daily Activities | Baseline and prior to Cycle 3 | To assess patient-reported pain severity and the impact of pain on daily activities before and during treatment with ganetespib and sirolimus. The Numerical Rating Scale-11 (NRS-11) will be used to assess pain severity. The NRS-11 is a self-report segmented 11-point numeric scale that assesses pain severity. It consists of a horizontal line with 0 representing "no pain" at the right end of the line and 10 representing "worst pain you can imagine" at the left end.The Brief Pain Inventory is a 7-item self-report questionnaire that measures the extent to which pain interferes with daily functioning. Patients are asked to indicate how much pain interfered with various activities in the past week, with scores ranging from 0 (does not interfere) to 10 (completely interferes). A total score is obtained by taking the mean of the scores for all 7 items; thus, the total pain interference score can range from 0 to 10. |
| Secondary | Utility of Three-dimensional MRI (3D-MRI) Analysis in Comparison to 1-dimensional and 2-dimensional Measurements | 4 months | To evaluate the utility of three-dimensional MRI (3D-MRI) analysis in comparison to 1-dimensional and 2-dimensional measurements as a method to more sensitively monitor response. |
| Secondary | Plasma Pharmacokinetic Profile of Ganetespib When Administered in Combination With Sirolimus | Cycle 1 Day 15 | To describe the plasma pharmacokinetic profile of ganetespib in terms of half life. |
| Secondary | Determine Maximum Tolerated Dose (MTD)/Recommended Dose (RD) of Ganetespib | Phase 1 of study | A conventional 3+3 dose escalation design was used for phase 1. All patients in phase 2 were treated with the recommended dose. |
Source ClinicalTrials.gov
Outcomes8
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus. | Toxicities will be evaluated over the first treatment cycle (each cycle=28 days) | 10 patients were enrolled in Phase 1 of the study to determine MTD/RD. Three patients were enrolled in the first dose level. Six patients were enrolled at dose level 2. 1 patient was inevaluable. | DLTs | NUMBER |
| PRIMARY | Clinical Benefit of Ganetespib in Combination With Sirolimus | Response evaluations will be performed after every 2 treatment cycles (each cycle=28 days) | 10 patients were enrolled in Phase 1 and 10 patients were enrolled in Phase 2 of the study. Overall number of patients enrolled was 20. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | 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 | 10 patients were enrolled in Phase 1 of the study. Three patients were enrolled in the first dose level. Six patients were enrolled at dose level 2. 1 patient was inevaluable. | ng/mL | MEAN |
| SECONDARY | Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells | Baseline and Cycle 1 Day 15 | 11 subjects provided consent and had adequate specimens for analysis. | ratio | MEAN |
| SECONDARY | Patient-reported Pain Severity and the Impact of Pain on Daily Activities | Baseline and prior to Cycle 3 | Thirteen subjects in phase 1 and phase 2 cohorts combined had MPNST and completed the pain evaluations. 4/13 subjects completed both baseline and pre-cycle 3 evaluations for pain. | units on a scale | MEAN |
| SECONDARY | Utility of Three-dimensional MRI (3D-MRI) Analysis in Comparison to 1-dimensional and 2-dimensional Measurements | 4 months | The 3D-MRI were not measurable with current modalities. Due to their nature and incomplete imaging, volumetric analysis was not feasible. | ||
| SECONDARY | Plasma Pharmacokinetic Profile of Ganetespib When Administered in Combination With Sirolimus | Cycle 1 Day 15 | 10 patients were enrolled in Phase 1 of the study. 1 patient was inevaluable. | hours | MEAN |
| SECONDARY | Determine Maximum Tolerated Dose (MTD)/Recommended Dose (RD) of Ganetespib | Phase 1 of study | 1 patient was inevaluable in Phase 1 of study. The recommended dose of ganetespib was determined to be 200 mg/m2 intravenously on days 1, 8, 15 with sirolimus 4mg orally once daily with a cycle 1 day 1 loading dose of 12mg. All patients in phase 2 were treated with the recommended dose. | Participants | COUNT_OF_PARTICIPANTS |
Source ClinicalTrials.gov
Results by group25
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus. | Ganetespib / Sirolimus | Dose Level 1 | 0 | DLTs | |
| Number of Dose Limiting Toxicities of Ganetespib When Administered in Combination With Sirolimus. | Ganetespib / Sirolimus | Dose Level 2 | 1 | DLTs | |
| Clinical Benefit of Ganetespib in Combination With Sirolimus | Ganetespib / Sirolimus | Phase 1 | 1 | Participants | |
| Clinical Benefit of Ganetespib in Combination With Sirolimus | Ganetespib / Sirolimus | Phase 2 | 0 | Participants | |
| Change in Plasma Pharmacokinetic Profile of Ganetespib and Sirolimus When Administered in Combination-Observed Maximum Plasma Concentration (Cmax) | Ganetespib / Sirolimus | Dose Level 1- Sirolimus trough | 12.1 | Standard Deviation 3.6 | ng/mL |
| Change in Plasma Pharmacokinetic Profile of Ganetespib and Sirolimus When Administered in Combination-Observed Maximum Plasma Concentration (Cmax) | Ganetespib / Sirolimus | Dose Level 2- Sirolimus trough | 12.5 | Standard Deviation 8.9 | ng/mL |
| Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells | Ganetespib / Sirolimus | Hsp70 at Baseline | 0.81 | Standard Deviation 0.39 | ratio |
| Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells | Ganetespib / Sirolimus | Hsp70 at Cycle 1 Day 15 | 0.84 | Standard Deviation 0.56 | ratio |
| Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells | Ganetespib / Sirolimus | pAKT at Baseline | 1.20 | Standard Deviation 0.70 | ratio |
| Changes in Pharmacodynamic Parameters in Peripheral Blood Mononuclear Cells | Ganetespib / Sirolimus | pAKT at Cycle 1 Day 15 | 1.44 | Standard Deviation 1.00 | ratio |
1 to 10 of 25Source ClinicalTrials.gov
See all 25 results by groupParticipant flow9
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Phase 1 Dose 1 | 3 | |
| Overall Study | STARTED | Phase 1 Dose 2 | 7 | |
| Overall Study | STARTED | Phase 2 | 10 | |
| Overall Study | COMPLETED | Phase 1 Dose 1 | 3 | |
| Overall Study | COMPLETED | Phase 1 Dose 2 | 6 | |
| Overall Study | COMPLETED | Phase 2 | 10 | |
| Overall Study | NOT COMPLETED | Phase 1 Dose 1 | 0 | |
| Overall Study | NOT COMPLETED | Phase 1 Dose 2 | 1 | |
| Overall Study | NOT COMPLETED | Phase 2 | 0 |
Source ClinicalTrials.gov
Adverse events321
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Abdominal pain | Gastrointestinal disorders | Phase 1 Dose 1 | 0 | 3 | 0 |
| other | Abdominal pain | Gastrointestinal disorders | Phase 1 Dose 2 | 0 | 7 | 0 |
| other | Abdominal pain | Gastrointestinal disorders | Phase 2 | 2 | 10 | 2 |
| other | Activated Partial Thromboplastin Time Prolonged | Investigations | Phase 1 Dose 1 | 0 | 3 | 0 |
| other | Activated Partial Thromboplastin Time Prolonged | Investigations | Phase 1 Dose 2 | 2 | 7 | 2 |
| other | Activated Partial Thromboplastin Time Prolonged | Investigations | Phase 2 | 3 | 10 | 3 |
| other | Alanine Aminotransferase increased | Investigations | Phase 1 Dose 1 | 1 | 3 | 3 |
| other | Alanine Aminotransferase increased | Investigations | Phase 1 Dose 2 | 1 | 7 | 2 |
| other | Alanine Aminotransferase increased | Investigations | Phase 2 | 2 | 10 | 8 |
| other | Alkaline Phosphatase increased | Investigations | Phase 1 Dose 1 | 1 | 3 | 1 |
1 to 10 of 321Source ClinicalTrials.gov
See all 321 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Phase 1 Dose 1 | 0 | 3 |
| Total, all-cause mortality | Phase 1 Dose 2 | 1 | 7 |
| Total, all-cause mortality | Phase 2 | 1 | 10 |
| Total, other adverse events | Phase 1 Dose 1 | 3 | 3 |
| Total, other adverse events | Phase 1 Dose 2 | 7 | 7 |
| Total, other adverse events | Phase 2 | 10 | 10 |
| Total, serious adverse events | Phase 1 Dose 1 | 1 | 3 |
| Total, serious adverse events | Phase 1 Dose 2 | 2 | 7 |
| Total, serious adverse events | Phase 2 | 6 | 10 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 32089640 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Source
- Release
- trials-2026-11-12-0.4.0
- Release manifest SHA-256
- 0f4a8d8c48aee2a7573ae0fa94ecbeab70c1adbe449bbc95c424bc7d3e97b9d4
- Registry capture
- 2026-11-12
- Results copy, AACT
- 2026-03-23
- NIH clinical studies file
- 2026-11-13
Source ClinicalTrials.gov
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNone stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT02008877
GET https://conductscience.org/api/trials/v1/NCT02008877/results?page=2