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Soft Tissue Sarcoma

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Gemcitabine

Docetaxel

Vorinostat

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Antimitotic Agents

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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

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

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

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)

administered on day 9 subcutaneously at 6 mg

Pegfilgrastim

Melissa Burgess, MD

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

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 of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma

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

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.

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.

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

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.

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.

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

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

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

Merck Sharp & Dohme LLC

Assistant Professor of Medicine Division of Hematology/Oncology

Additional information: Six of the twelve patients enrolled to the Phase 1b group at Dose Level 1 / RP2D were analyzed with the Phase 2 group due to same dose level of vorinostat.

Dose Level 1:

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

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).

Vorinostat: 300 mg daily given orally 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).

Pegfilgrastim: Administered on day 9 subcutaneously at 6 mg.

Docetaxel + Gemcitabine + Pegfilgrastim + Vorinostat 300 mg/Day

Dose Level 2:

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

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).

Vorinostat: 200 mg twice daily given orally 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).

Pegfilgrastim: Administered on day 9 subcutaneously at 6 mg.

Docetaxel + Gemcitabine + Pegfilgrastim + Vorinostat 200 mg Twice/Day

Dose Level 1

Dose Level 2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Barbara M Stadterman, MPH, MCCR, Clinical Trials Administrator

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

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.

Vorinostat: given orally at either 300 mg/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).

Pegfilgrastim: Administered on day 9 subcutaneously at 6 mg.

Combination Therapy: Docetaxel + Gemcitabine + Vorinostat + Pegfilgrastim

Patients treated with combination therapy.

Phase I: Recommended Phase II Dose of Vorinostat

Dose Level 1:

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

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).

Vorinostat: RP2D - 300 mg daily given orally 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).

Pegfilgrastim: Administered on day 9 subcutaneously at 6 mg.

Phase 2

Patients that received combination therapy that were evaluable for response to treatment.

Note: Six of the twelve patients enrolled to the Phase 1b group at Dose Level 1 / RP2D were analyzed with the Phase 2 group due to same dose level of vorinostat.

Six-month Progression-free Survival (PFS)

Dose Level 1:

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

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).

Vorinostat: RP2D - 300 mg/day given orally 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).

Pegfilgrastim: Administered on day 9 subcutaneously at 6 mg.

Patients that received combination therapy. Note: Six of the twelve patients enrolled to the Phase 1b group at Dose Level 1 / RP2D were analyzed with the Phase 2 group due to same dose level of vorinostat.

Objective Response Rate (ORR)

Progression-free Survival (PFS)

One-year Progression-free Survival (PFS)

Overall Survival (OS)

Six-month Overall Survival (OS)

One-year Overall Survival (OS)

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

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.

Vorinostat: given orally at Dose level 1 (300 mg/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).

Pegfilgrastim: Administered on day 9 subcutaneously at 6 mg.

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

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.

Vorinostat: given orally at Dose level 2 (200 mg twice/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).

Pegfilgrastim: Administered on day 9 subcutaneously at 6 mg.

Phase 1b

Camptothecin

Pegamotecan

The purpose of this study is to evaluate the safety and efficacy of Pegamotecan (Peg-Camptothecin) in patients with Advanced or Metastatic Soft Tissue sarcoma.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma	NCT01879085	Sarcoma	Docetaxel Gemcitabine Vorinostat Pegfilgrastim	18 Years -	University of Pittsburgh
Efficacy and Safety Evaluation of Pegamotecan (PEG-camptothecin) in Advanced or Metastatic Soft Tissue Sarcoma	NCT00079950	Sarcoma, Soft T...	Pegamotecan	18 Years -	Enzon Pharmaceuticals, Inc.
Efficacy and Safety Evaluation of Pegamotecan (PEG-camptothecin) in Advanced or Metastatic Soft Tissue Sarcoma	NCT00079950	Sarcoma, Soft T...	Pegamotecan	18 Years -	Enzon Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for soft

Every month we try and update this database with for soft cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for soft

Every month we try and update this database with for soft cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for soft cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.