PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of PXD101 and 17-AAG administered to patients with refractory solid tumor malignancies. II. To determine the maximum tolerated dose (MTD) and recommended phase II dose of PXD101 and 17-AAG in patients with refractory solid tumor malignancies. SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetics of PXD101 and 17-AAG in patients receiving this combination. II. To evaluate the antitumor activity of this combination, per tumor measurements using the RECIST criteria. TERTIARY OBJECTIVES: I. To evaluate the effect of treatment with PXD101 and 17-AAG on the transcriptional upregulation of targeted genes in tumor and surrogate tissue (PBMCs) by means of RTPCR and incorporation of the chromatin immunoprecipitation assay. II. To evaluate the effect of this combination treatment on the post translational modification of histones from tumor and surrogate tissue (PBMCs). OUTLINE: This is a dose-escalation study. Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 2 hours on days 1, 4, 8, and 11 and PXD101 IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-AAG and PDX101 until the maximum tolerated dose (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. Up to 12 patients are treated at the MTD. Patients undergo blood collection on days 1 and 4 of course 1 for pharmacokinetic studies. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.