Phase 2
Completed N=12
Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
Source: ClinicalTrials.gov NCT01879085 ↗Enrolled (actual)
12
Serious AEs
59.5%
Results posted
Sep 2022
Primary outcomePrimary: Phase I: Recommended Phase II Dose of Vorinostat — 300 mg/day of Vorinostat
Summary
This is a Phase Ib/II experimental, open-label, dose escalation, active treatment study designed to determine the safety, tolerability, and recommended dose of the combination.
During the Phase 2 portion of the study, we will assess progression-free survival (PFS), overall survival (OS),overall response rate (ORR), correlative endpoints, DNA methylation measured by microarray, and expression level of the genes as measured by microarray
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase I: Recommended Phase II Dose of Vorinostat |
300 | — |
| PRIMARY Six-month Progression-free Survival (PFS) |
0.473 | — |
| SECONDARY Objective Response Rate (ORR) |
7 | — |
| SECONDARY Progression-free Survival (PFS) |
5.552361 | — |
| SECONDARY One-year Progression-free Survival (PFS) |
0.304 | — |
| SECONDARY Overall Survival (OS) |
11.92608 | — |
| SECONDARY Six-month Overall Survival (OS) |
0.742 | — |
| SECONDARY One-year Overall Survival (OS) |
0.477 | — |
Eligibility Criteria
Inclusion Criteria
- Patients must have histologically confirmed soft tissue sarcoma with evidence of metastatic or unresectable disease.
- Patients must have measurable disease by RECIST 1.1.
- Up to 32 prior cytotoxic chemotherapy regimens in the metastatic setting are allowed. Adjuvant chemotherapy or targeted therapy will not be considered a prior line of treatment.
- Age ≥18 years.
- ECOG performance status ≤2 (Karnofsky ≥60%).
- Life expectancy of greater than 12 weeks.
- Patients must have normal organ and marrow function as defined below:
- leukocytes ≥3,000/µL
- absolute neutrophil count ≥1,500/µL
- platelets ≥100,000/µL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) ≤1.5 X institutional upper limit of normal (ULN)
- creatinine ≤1.5 X institutional upper limit of normal (ULN)
- Peripheral neuropathy, if present, should be ≤grade 1.
- Women of Child bearing potential MUST use contraceptives.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- The following specific histologic subtypes of soft tissue sarcomas will be excluded: GIST, Kaposi's sarcoma, mesothelioma, dermatofibrosarcoma, chordoma, alveolar soft-part sarcoma. Also, all bone sarcomas are excluded including Ewing's sarcoma, osteosarcoma, GIST, low grade chondrosarcoma, and chordoma.
- Patients who have had treatment with chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients who are receiving any other investigational agents.
- Patients with known brain metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, docetaxel, vorinostat, or G-CSF.
- Patients who have received and progressed on the combination of gemcitabine and docetaxel in the metastatic setting.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and breastfeeding women
- Patients taking concomitant HDAC inhibitors.
- HIV-positive patients on combination antiretroviral treatment
Data sourced from ClinicalTrials.gov (NCT01879085). 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. Informational only — not medical advice.