Back to results

Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma (GemTax)

Primary Purpose

Sarcoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Docetaxel

Gemcitabine

Vorinostat

Pegfilgrastim

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring advanced, metastatic, unresectable, soft, tissue, sarcomas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hillman Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combination therapy

Arm Description

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Objective Response Rate (ORR)

Number of patients with Complete response [CR] + partial response [PR], per RECIST v1.1 criteria . Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to <10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

Progression-free Survival (PFS)

The median length of time from the beginning of study treatment that patients remain alive without progression of their disease (cancer). 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 (this 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.

One-year Progression-free Survival (PFS)

Proportion of participants whose disease does not progress within one year of start of treatment (number of patients with 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.

Overall Survival (OS)

The median length of time from the start of treatment that diagnosed study participants remain alive.

Six-month Overall Survival (OS)

Proportion of participants alive at six months from the start of treatment.

One-year Overall Survival (OS)

Proportion of participants alive at one year from the start of treatment.

Full Information

NCT ID

NCT01879085

First Posted

May 20, 2013

Last Updated

August 24, 2022

Sponsor

Melissa Burgess, MD

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01879085

Brief Title

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

Acronym

GemTax

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

September 24, 2013 (Actual)

Primary Completion Date

April 15, 2021 (Actual)

Study Completion Date

April 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Melissa Burgess, MD

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcoma

Keywords

advanced, metastatic, unresectable, soft, tissue, sarcomas

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Combination therapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Taxotere

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar

Intervention Description

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

Intervention Name(s)

Vorinostat

Other Intervention Name(s)

Zolinza

Intervention Description

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

Intervention Name(s)

Pegfilgrastim

Other Intervention Name(s)

Neulasta

Intervention Description

administered on day 9 subcutaneously at 6 mg

Primary Outcome Measure Information:

Title

Phase I: Recommended Phase II Dose of Vorinostat

Description

Time Frame

During Cycle 1 of treatment

Title

Six-month Progression-free Survival (PFS)

Description

Time Frame

Up to 6 months (per patient)

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

Time Frame

Up to 7 years and 7 months

Title

Progression-free Survival (PFS)

Description

Time Frame

Up to 7 years and 7 months

Title

One-year Progression-free Survival (PFS)

Description

Time Frame

Up to one year (per patient)

Title

Overall Survival (OS)

Description

The median length of time from the start of treatment that diagnosed study participants remain alive.

Time Frame

Up to 7 years and 7 months

Title

Six-month Overall Survival (OS)

Description

Proportion of participants alive at six months from the start of treatment.

Time Frame

Up to 6 months (per patient)

Title

One-year Overall Survival (OS)

Description

Proportion of participants alive at one year from the start of treatment.

Time Frame

Up to one year (per patient)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Melissa Burgess, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hillman Cancer Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs