Phase 1b/2 Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma

• Status: Active, not recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Melissa Burgess, MD
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Docetaxel; Gemcitabine; Vorinostat

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