Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma

NCT ID: NCT01879085

Last Updated: 2022-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-24
• Study Completion Date: 2021-04-15

Brief 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

Detailed Description

Phase 1b

• To determine the dose of vorinostat that can be safely combined with gemcitabine and docetaxel in patients with advanced sarcomas.
• To characterize the Pharmacokinetics (PK) and Pharmacodynamics (PD) of vorinostat when combined with gemcitabine and docetaxel in patients with advanced sarcomas (Exploratory Aim).

Phase 2

• To determine the safety and efficacy of gemcitabine and docetaxel in combination with vorinostat in patients with advanced sarcomas. The hypothesis is that gemcitabine and docetaxel + vorinostat will be safe and will improve the 6-months progression-free rates (PFR) of the combination by 20% (from 20% to 40%).
• To determine the objective response rate, progression-free, and overall survival of patients with advanced sarcomas treated with gemcitabine and docetaxel + vorinostat;
• To develop a predictive molecular signature of response to treatment in advanced sarcomas.

Conditions

Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination therapy

Dose Level\\Docetaxel IV\\ Gemcitabine IV\\Vorinostat PO\\Pegfilgrastim 1\\75 mg/m2\\900 mg/m2\\300 mg once daily\\6 mg on day 9 2\\75 mg/m2\\900 mg/m2\\200 mg twice daily\\6 mg on day 9 3\\75 mg/m2\\900 mg/m2\\300 mg twice daily\\6 mg on day 9 4\\75 mg/m2\\900 mg/m2\\400 mg twice daily\\6 mg on day 9

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

75 mg/m2 IV given over 60 minutes on day 8 every 21 days (1 cycle)

Gemcitabine

Intervention Type: DRUG

given on days 1 and 8 at 900 mg/m2 IV over 90 minutes (fixed dose infusion rate at 10 mg/m2/min) every 21 days (1 cycle). For dose level -2, given over 67.5 minutes at 10 mg/m2/min

Vorinostat

Intervention Type: DRUG

given orally at the specified dose levels (either 300 mg/daily or 200 mg twice per day) on days -1 to +2 and days +7-9 every 21 days (treatment for 3 days starting one day prior to chemotherapy on every cycle)

Pegfilgrastim

Intervention Type: DRUG

administered on day 9 subcutaneously at 6 mg

Interventions

Docetaxel

75 mg/m2 IV given over 60 minutes on day 8 every 21 days (1 cycle)

Intervention Type: DRUG

Gemcitabine

given on days 1 and 8 at 900 mg/m2 IV over 90 minutes (fixed dose infusion rate at 10 mg/m2/min) every 21 days (1 cycle). For dose level -2, given over 67.5 minutes at 10 mg/m2/min

Intervention Type: DRUG

Vorinostat

given orally at the specified dose levels (either 300 mg/daily or 200 mg twice per day) on days -1 to +2 and days +7-9 every 21 days (treatment for 3 days starting one day prior to chemotherapy on every cycle)

Intervention Type: DRUG

Pegfilgrastim

administered on day 9 subcutaneously at 6 mg

Intervention Type: DRUG

Other Intervention Names

Taxotere; Gemzar; Zolinza; Neulasta

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Melissa Burgess, MD

OTHER

Sponsor Role: lead

Responsible Party

Melissa Burgess, MD

Assistant Professor of Medicine Division of Hematology/Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Melissa Burgess, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UPCI# 12-104

Identifier Type: -

Identifier Source: org_study_id