Doxorubicin Hydrochloride and Alvocidib in Treating Patients With Metastatic or Recurrent Sarcoma That Cannot Be Removed By Surgery
Gastrointestinal Stromal Tumor, Recurrent Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma
About this trial
This is an interventional treatment trial for Gastrointestinal Stromal Tumor
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed soft-tissue sarcoma* Unresectable disease Locally recurrent or metastatic disease Disease amenable to biopsy (patients treated at the maximum tolerated dose only) No known prior or concurrent brain metastases Performance status - Karnofsky 60-100% Performance status - ECOG 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 mg/dL AST and ALT ≤ 2.5 times upper limit of normal Creatinine ≤ 1.5 mg/dL Creatinine clearance ≥ 60 mL/min Ejection fraction ≥ 50% by MUGA or echocardiogram No uncontrolled hypertension No myocardial infarction No New York Heart Association class II-IV congestive heart failure No unstable angina No serious cardiac arrhythmia requiring medication No peripheral vascular disease ≥ grade 2 within the past year No other clinically significant cardiac disease No prior deep vein thrombosis No other prior vascular thrombus No prior pulmonary embolism Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No symptomatic peripheral neuropathy ≥ grade 2 No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix Carcinoma in situ not considered a second malignancy No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection No other uncontrolled illness See Chemotherapy At least 3 weeks since prior immunotherapy and recovered At least 3 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) and recovered No more than 2 prior cytotoxic chemotherapy regimens Peroxisome proliferator-activated receptor (PPAR)-gamma agonists, thalidomide, or targeted therapy (i.e., tyrosine kinase inhibitors including imatinib mesylate, sorafenib, or sunitinib malate) do not count as a prior chemotherapy regimen No prior anthracyclines At least 3 weeks since prior radiotherapy and recovered No prior extensive radiotherapy to bone marrow-producing sites (e.g., radiotherapy to both the pelvis and spine) At least a 1 week washout period since prior tyrosine kinase inhibitors or other targeted therapy Concurrent low-dose warfarin (1 mg per day) to prevent thrombus of a central line allowed No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer therapy
Sites / Locations
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Experimental
Treatment (chemotherapy)
Patients receive doxorubicin hydrochloride IV over 5-10 minutes and alvocidib IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients reaching a cumulative doxorubicin dose of 600 mg/m^2 or experiencing cardiotoxicity may receive alvocidib alone at the discretion of the investigator. Cohorts of 3-6 patients receive escalating doses of alvocidib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Ten additional patients receive treatment at the MTD. Patients are followed every 3 months for 1 year.