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

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