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Vorinostat, Gemcitabine Hydrochloride, and Docetaxel in Treating Patients with Soft Tissue Sarcoma That is Metastatic or Cannot Be Removed By Surgery

Trial Status: Active

This phase I / II trial studies the side effects and best dose of vorinostat when given together with gemcitabine hydrochloride and docetaxel and to see how well they work in treating patients with soft tissue sarcoma that has spread to other places in the body (metastatic) or cannot be removed by surgery. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat with combination chemotherapy may kill more tumor cells than giving either one alone.

Inclusion Criteria

  • Patients must have histologically confirmed soft tissue sarcoma with evidence of metastatic or unresectable disease
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; at least one measurable lesion needs to be outside the field of prior therapeutic radiation or has progressed after radiation
  • Up to 3 prior cytotoxic chemotreatment regimens in the metastatic setting are allowed; adjuvant chemotreatment will not be considered a prior line of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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
  • The effects of vorinostat on the developing human fetus are unknown; for this reason and because the other chemotherapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 4 months after completion of study drug administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; if pregnancy is confirmed, the patient will be deemed not eligible or if started will be immediately removed from study; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration
  • 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: gastrointestinal stromal tumor (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 should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, docetaxel, vorinostat, or granulocyte colony-stimulating factor (G-CSF)
  • Patients who have received the combination of gemcitabine and docetaxel in the metastatic setting are excluded
  • 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 are excluded from this study
  • Patients taking concomitant histone deacetylase (HDAC) inhibitors; use of HDAC inhibitor like compounds such as valproic acid for epilepsy is permitted if there is at least a 2 week wash out
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral treatment are ineligible because of the potential for pharmacokinetic interactions with vorinostat, gemcitabine, and docetaxel; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive treatment; appropriate studies will be undertaken in patients receiving combination antiretroviral treatment when indicated


University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE
Contact: Melissa Amber (Moidel) Burgess
Phone: 412-623-7277


I. To determine the dose of vorinostat that can be safely combined with gemcitabine (gemcitabine hydrochloride) and docetaxel in patients with advanced sarcomas. (Phase Ib)

II. To determine the safety and efficacy of gemcitabine and docetaxel in combination with vorinostat in patients with advanced sarcomas. (Phase II)


I. To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of vorinostat when combined with gemcitabine and docetaxel in patients with advanced sarcomas. (Phase Ib)

II. To determine the objective response rate, progression-free and overall survival of patients with advanced sarcomas treated with gemcitabine and docetaxel + vorinostat. (Phase II)

II. To develop a predictive molecular signature of response to chemotreatment in advanced sarcomas. (Phase II)

OUTLINE: This is a phase I, dose-escalation of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) once daily (QD) or twice daily (BID) on days -1 to 2 and 7-9, gemcitabine hydrochloride intravenously (IV) over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 6 months.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
University of Pittsburgh Cancer Institute (UPCI)

Principal Investigator
Melissa Amber (Moidel) Burgess

  • Primary ID 12-104
  • Secondary IDs NCI-2013-01735, UPCI 12-104
  • ID NCT01879085