Phase II Trial of Depsipeptide (NSC-630176) in Colorectal Cancer Patients Who Have Received Either One or Two Chemotherapy Regimens for Metastatic or Locally Advanced, Unresectable Disease

Histologically or cytologically verified colorectal cancer. Distant metastatic dz or locally advanced dz that is not surgically resectable. Measurable dz. Must have received either one or two prior chemo regimens for metastatic or locally advanced, unresectable dz: (1) If pt received adjuvant tx with oxaliplatin-based regimen, they must have had exactly one regimen for metastatic or locally advanced, unresectable disease, and this must not have been oxaliplatin-based. (2) If pt received adjuvant tx with irinotecan-based regimen, they must have had exactly one regimen for metastatic or locally advanced, unresectable dz, and this must not have been irinotecan-based. (3) If pt did not receive adjuvant tx with an oxaliplatin- or inrinotecan-based regimen, they must have had either one or two regimens for metastatic or locally advanced, unresectable dz. Must be at least 28 days beyond chemo, radiation therapy and/or surgery, and recovered from effects. No prior depsipeptide. Must not be receiving any other agents known to have histone deacetylase inhibitor activity. No significant cardiac dz. Within 14 days prior to reg: WBC greater than or equal to 3,000/�l; ANC greater than or equal to 1,500/�l; platelets greater than or equal to 100,000/�l. Within 28 days prior to reg: serum creatinine less than or equal to IULN; bilirubin less than or equal to IULN; SGOT/SGPT less than or equal to 2.5 x IULN; potassium greater than or equal to 4 mmol/L; magnesium greater than or equal to 2 mg/dL. Must not be taking hydrochlorothiazide. Performance status 0-1. HIV-positive pts receiving combination anti-retroviral tx are not eligible. No known brain metastases. No history of allergic reactions to compounds of similar chemical or biological composition to depsipeptide. No plans for concurrent tx for cancer while on protocol. No pregnant or nursing women. Pts of reproductive potential must have agreed to use effective contraceptive method. No prior malignancy except adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer from which pt has been disease-free for 5 yrs.