SarcomaPhase 1/2GemTaxNCT01879085
Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
A Phase 1/2 study testing Docetaxel, Gemcitabine and Vorinostat in people with Sarcoma, run by Melissa Burgess, MD at 1 site in United States.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma
- What is being tested?
- Docetaxel, Gemcitabine and Vorinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Sep 2013to 15 Apr 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase 1b/2 Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
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
Read the 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
- Being tested
- Docetaxel, Gemcitabine, Vorinostat, Pegfilgrastim
- Keywords
- advanced, metastatic, unresectable, soft, tissue, sarcomas
- Medical subject headings
- Sarcoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Also called Taxotere
75 mg/m2 IV given over 60 minutes on day 8 every 21 days (1 cycle)
GemcitabineDrug
Also called Gemzar
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
VorinostatDrug
Also called Zolinza
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)
PegfilgrastimDrug
Also called Neulasta
administered on day 9 subcutaneously at 6 mg
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Docetaxel; Drug: Gemcitabine; Drug: Vorinostat; Drug: Pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 6 months (per patient)
Secondary outcomes (6)
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
Measured: Up to 7 years and 7 months
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.
Measured: Up to 7 years and 7 months
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.
Measured: Up to one year (per patient)
Overall Survival (OS)
The median length of time from the start of treatment that diagnosed study participants remain alive.
Measured: Up to 7 years and 7 months
Six-month Overall Survival (OS)
Proportion of participants alive at six months from the start of treatment.
Measured: Up to 6 months (per patient)
One-year Overall Survival (OS)
Proportion of participants alive at one year from the start of treatment.
Measured: Up to one year (per patient)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2013 (estimated)
- Study start24 Sep 2013
- Primary completion15 Apr 2021
- Study completion15 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Melissa Burgess, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Melissa Burgess, MD, University of Pittsburgh
- Investigators
- Melissa Burgess, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01879085
- Sponsor's protocol ID
- UPCI# 12-104
- Acronym
- GemTax
- Status last verified
- Aug 2022
- First submitted
- 20 May 2013
- Last updated
- 21 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b/2 Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma
- ClinicalTrials.gov ID
- NCT01879085
- Acronym / sponsor ID
- GemTax / UPCI# 12-104
- Conditions
- Sarcoma
- Keywords
- advanced, metastatic, unresectable, soft, tissue, sarcomas
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Melissa Burgess, MDUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 24 Sep 2013 (actual)
- Primary completion
- 15 Apr 2021 (actual)
- Study completion
- 15 Apr 2021 (actual)
- First posted
- 17 Jun 2013 (estimated)
- Results
- Posted 21 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination therapy | Experimental | Drug: Docetaxel, Drug: Gemcitabine, Drug: Vorinostat, Drug: PegfilgrastimDose 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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%).
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DocetaxelAlso: Taxotere75 mg/m2 IV given over 60 minutes on day 8 every 21 days (1 cycle) | Drug | Combination therapy |
| GemcitabineAlso: Gemzargiven 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 | Drug | Combination therapy |
| VorinostatAlso: Zolinzagiven 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) | Drug | Combination therapy |
| PegfilgrastimAlso: Neulastaadministered on day 9 subcutaneously at 6 mg | Drug | Combination therapy |
Primary outcome
Phase I: Recommended Phase II Dose of Vorinostat
Time frame: During Cycle 1 of treatment
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)
Time frame: Up to 6 months (per patient)
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.
6 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to 7 years and 7 months
Progression-free Survival (PFS)
Time frame: Up to 7 years and 7 months
One-year Progression-free Survival (PFS)
Time frame: Up to one year (per patient)
Overall Survival (OS)
Time frame: Up to 7 years and 7 months
Six-month Overall Survival (OS)
Time frame: Up to 6 months (per patient)
One-year Overall Survival (OS)
Time frame: Up to one year (per patient)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melissa Burgess, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Docetaxel, Gemcitabine and Vorinostat in people with Sarcoma, run by Melissa Burgess, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Recommended Phase II Dose of Vorinostat (time frame: During Cycle 1 of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2022.