Clinical Trials /

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

NCT01879085

Description:

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

Related Conditions:
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1b/2 Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
  • Official Title: Phase 1b/2 Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: UPCI# 12-104
  • NCT ID: NCT01879085

Conditions

  • Sarcoma

Interventions

DrugSynonymsArms
DocetaxelTaxotereCombination therapy
GemcitabineGemzarCombination therapy
VorinostatZolinzaCombination therapy
PegfilgrastimNeulastaCombination therapy

Purpose

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.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Combination therapyExperimentalDose 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
  • Docetaxel
  • Gemcitabine
  • Vorinostat
  • Pegfilgrastim

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:To determine the dose of vorinostat that can be safely combined with gemcitabine and docetaxel in patients with advanced sarcomas

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Melissa Burgess, MD

Trial Keywords

  • advanced
  • metastatic
  • unresectable
  • soft
  • tissue
  • sarcomas

Last Updated

July 18, 2016