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

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ClinicalTrials.gov Identifier: NCT01879085
Recruitment Status : Recruiting
First Posted : June 17, 2013
Last Update Posted : July 11, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Melissa Burgess, MD, University of Pittsburgh

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


Condition or disease Intervention/treatment Phase
Sarcoma Drug: Docetaxel Drug: Gemcitabine Drug: Vorinostat Drug: Pegfilgrastim Phase 1 Phase 2

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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 67 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b/2 Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
Study Start Date : June 2013
Estimated Primary Completion Date : February 1, 2020
Estimated Study Completion Date : August 1, 2020


Arm Intervention/treatment
Experimental: 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
Drug: Docetaxel
75 mg/m2 IV over 60 minutes on day 8 every 21 days (1 cycle).
Other Name: Taxotere

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, Gem will be given over 67.5 minutes at 10 mg/m2/min.
Other Name: Gemzar

Drug: Vorinostat
will be given orally at the specified dose levels (Table 2) 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).
Other Name: Zolinza

Drug: Pegfilgrastim
Administered on day 9 subcutaneously at 6 mg.
Other Name: Neulasta




Primary Outcome Measures :
  1. For phase 1 portion: To determine the safety, tolerability, and Phase 2 recommended dose (RP2D) of the combination. [ Time Frame: 5 years or until disease progression/survival ]
    To determine the dose of vorinostat that can be safely combined with gemcitabine and docetaxel in patients with advanced sarcomas

  2. For phase 2 portion: Six-month progression-free survival rate (PFR). [ Time Frame: six months progression-free survival ]
    To determine the safety and efficacy of gemcitabine and docetaxel in combination with vorinostat in patients with advanced sarcomas using the Phase 2 recommended dose (RP2D).


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 5 years or until disease progression/survival ]
    To determine the safety, tolerability, and Phase 2 recommended dose (RP2D) of the combination. Six-month progression-free survival rate (PFR).

  2. Overall survival (OS) [ Time Frame: 5 years or until disease progression/survival ]
    To determine the safety, tolerability, and Phase 2 recommended dose (RP2D) of the combination. Six-month progression-free survival rate (PFR).

  3. Overall response rate (ORR) as determined by RECIST criteria. [ Time Frame: 5 years or until disease progression/survival ]
    To determine the safety, tolerability, and Phase 2 recommended dose (RP2D) of the combination. Six-month progression-free survival rate (PFR).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01879085


Locations
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United States, California
Sarcoma Oncology Center Not yet recruiting
Santa Monica, California, United States, 90403
Contact: Sant Chawla, MD    310-552-9999    santchawla@sarcomaoncology.com   
Contact: Victoria Chua    (310) 552-9999    vchua@sarcomaoncology.com   
Principal Investigator: Sant Chawla, MD         
United States, Pennsylvania
Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Melissa Burgess, MD    412-623-7277    burgessma@upmc.edu   
Principal Investigator: Melissa Burgess, MD         
Sponsors and Collaborators
Melissa Burgess, MD
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Melissa Burgess, MD University of Pittsburgh

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Responsible Party: Melissa Burgess, MD, Assistant Professor of Medicine Division of Hematology/Oncology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01879085    
Other Study ID Numbers: UPCI# 12-104
First Posted: June 17, 2013    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Keywords provided by Melissa Burgess, MD, University of Pittsburgh:
advanced
metastatic
unresectable
soft
tissue
sarcomas
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Docetaxel
Vorinostat
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Histone Deacetylase Inhibitors