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

NCT01879085 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: UPCI# 12-104
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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

Conditions

Sarcoma

Keywords

advanced; metastatic; unresectable; soft; tissue; sarcomas

Outcome Measures

Primary Outcomes (2)

• Phase I: Recommended Phase II Dose of Vorinostat

  Recommended Phase ll dose of vorinostat that can be safely combined with gemcitabine and docetaxel. Gemcitabine and docetaxel were given at a fixed dose while vorinostat was dose-escalated using a standard '3+3' design. Dose-limiting toxicity (DLT) is defined as specific study drug-related events experienced during Cycle 1; only DLTs observed in a patient during the first cycle of treatment will be used for the dose escalation decision.

  During Cycle 1 of treatment

• Six-month Progression-free Survival (PFS)

  Proportion of participants whose disease does not progress within 6 months of start of treatment (number of patients without progressive disease/total number of patients). Per RECIST v1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.

  Up to 6 months (per patient)

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Up to 7 years and 7 months

• Progression-free Survival (PFS)

  Up to 7 years and 7 months

• One-year Progression-free Survival (PFS)

  Up to one year (per patient)

• Overall Survival (OS)

  Up to 7 years and 7 months

• Six-month Overall Survival (OS)

  Up to 6 months (per patient)

Study Arms (1)

Combination therapy

EXPERIMENTAL

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; Drug: Gemcitabine; Drug: Vorinostat; Drug: Pegfilgrastim

Interventions

Docetaxel DRUG

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

Also known as: Taxotere

Combination therapy

Gemcitabine 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

Also known as: Gemzar

Combination therapy

Vorinostat 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)

Also known as: Zolinza

Combination therapy

Pegfilgrastim DRUG

administered on day 9 subcutaneously at 6 mg

Also known as: Neulasta

Combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Melissa Burgess, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Sarcoma; Neoplasm Metastasis

Interventions

Docetaxel; Gemcitabine; Vorinostat; pegfilgrastim

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Barbara M Stadterman, MPH, MCCR, Clinical Trials Administrator
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Melissa Burgess, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine Division of Hematology/Oncology

Study Record Dates

• First Submitted: May 20, 2013
• First Posted: June 17, 2013
• Study Start: September 24, 2013
• Primary Completion: April 15, 2021
• Study Completion: April 15, 2021
• Last Updated: September 21, 2022
• Results First Posted: September 21, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)