Overview

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