bcx-1777 in treating patients with refractory cancer

Conditions: Cancer

Summary: rationale: bcx-1777 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. purpose: phase i trial to study the effectiveness of bcx-1777 in treating patients who have refractory cancer.

objectives: primary * determine the maximum tolerated dose of bcx-1777 in patients with refractory t-cell or non-t-cell malignancies. * determine the safety and dose-limiting toxicity of this drug in these patients. secondary * determine the pharmacokinetics of single oral and single and multiple iv doses of this drug in these patients. * determine the oral bioavailability of this drug in these patients. * determine, preliminarily, the antitumor activity of this drug in these patients. outline: this is an open-label, nonrandomized, dose-escalation, multicenter study. * courses 1 and 2: patients receive oral bcx-1777 on days 1 and 15\* and bcx-1777 iv over 30 minutes on days 8\* and 22\*. * course 3: beginning approximately 6 days\* after the completion of courses 1 and 2, patients receive bcx-1777 iv over 30 minutes once daily on days 1-5 and 8-12 (total of 10 doses). note: \*+/- 1 day patients with stable disease or better and no dose-limiting toxicity (dlt) may receive an additional 10-dose treatment course (as in course 3) after a 10- to 16-day drug-free interval. treatment continues in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of bcx-1777 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 dlt. patients are followed at 14 and 30 days. projected accrual: a total of 3-24 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed diagnosis of 1 of the following: * hematologic malignancy that is refractory to at least 1 prior curative treatment * non-hematologic tumor that is refractory to at least 2 prior therapies, with or without measurable disease, including the following: * gastrointestinal adenocarcinoma of 1 of the following sites: * pancreatic * biliary * gastric * colorectal * esophageal * melanoma * ovarian cancer * astrocytoma brain tumor * not immediately eligible for any other treatment that would be potentially curative or life-prolonging, in the opinion of the investigator * patients who may be candidates for future bone marrow transplantation are eligible * no brain metastases (other than astrocytomas) * no clinically significant pleural effusion * no complete tumor obstruction (e.g., bronchus, ureter, or bowel) patient characteristics: age * 18 and over performance status * ecog 0-2 or * karnofsky 50-100% life expectancy * not specified hematopoietic * wbc at least 3,500/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count greater than 50,000/mm\^3 * hematocrit stable without the need for transfusion (epoetin alfa support allowed) hepatic * bilirubin less than 1.5 times upper limit of normal (uln) (unless due to gilbert's syndrome) * sgot and sgpt less than 2 times uln * no active hepatitis b or c renal * creatinine clearance at least 50 ml/min cardiovascular * no american heart association class iii or iv cardiac disease other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv negative * no active systemic infection requiring iv antibiotics prior concurrent therapy: biologic therapy * not specified chemotherapy * not specified endocrine therapy * concurrent corticosteroids allowed provided the patient is on a stable regimen radiotherapy * not specified surgery * not specified other * recovered from prior therapy * no grade 2-4 toxicity * more than 3 weeks since prior antineoplastic and/or investigational therapy * no other concurrent systemic antineoplastic or investigational therapy

Keywords: acute undifferentiated leukemia anaplastic large cell lymphoma angioimmunoblastic t-cell lymphoma atypical chronic myeloid leukemia, bcr-abl1 negative chronic eosinophilic leukemia primary myelofibrosis chronic myelomonocytic leukemia chronic neutrophilic leukemia essential thrombocythemia intraocular lymphoma myelodysplastic/myeloproliferative neoplasm, unclassifiable polycythemia vera previously treated myelodysplastic syndromes primary central nervous system non-hodgkin lymphoma prolymphocytic leukemia recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia recurrent adult t-cell leukemia/lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult burkitt lymphoma recurrent adult hodgkin lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent mycosis fungoides/sezary syndrome refractory chronic lymphocytic leukemia refractory hairy cell leukemia refractory multiple myeloma relapsing chronic myelogenous leukemia secondary acute myeloid leukemia secondary myelodysplastic syndromes waldenström macroglobulinemia adenocarcinoma of the colon adenocarcinoma of the esophagus adenocarcinoma of the pancreas adenocarcinoma of the rectum recurrent adult brain tumor recurrent adult primary liver cancer recurrent colon cancer recurrent esophageal cancer recurrent gastric cancer recurrent melanoma recurrent ovarian epithelial cancer recurrent pancreatic cancer recurrent rectal cancer adenocarcinoma of the stomach adult anaplastic astrocytoma adult glioblastoma adult pilocytic astrocytoma adult subependymoma adenocarcinoma of the extrahepatic bile duct recurrent extrahepatic bile duct cancer recurrent cutaneous t-cell non-hodgkin lymphoma de novo myelodysplastic syndromes recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone b-cell lymphoma splenic marginal zone lymphoma adult acute myeloid leukemia with t(8;21)(q22;q22) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with 11q23 (mll) abnormalities adult acute myeloid leukemia with t(15;17)(q22;q12) adult diffuse astrocytoma adult giant cell glioblastoma adult gliosarcoma t-cell large granular lymphocyte leukemia