BCX-1777 in Treating Patients With Refractory Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I Pharmacology Study Of Oral And Intravenous BCX-1777 In Patients With Refractory T-Cell And Non-T-Cell Malignancies

Conditions
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Cancer

Intervention / Treatment
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* Drug: forodesine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: forodesine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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