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.

Condition	Treatment or Intervention	Phase
central nervous system cancer female reproductive cancer Gastrointestinal Cancer hematopoietic and lymphoid cancer skin tumor	Drug: BCX-1777  Procedure: enzyme inhibitor therapy	Phase I

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*.
• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States

Study chairs or principal investigators

Alex Shalaurov, MD,  Study Chair,  Inveresk Research Group, Incorporated   

Study ID Numbers:  CDR0000341332; BIOCRYST-1777BC-101; CCF-5909
Record last reviewed:  August 2004
Record first received:  December 10, 2003
ClinicalTrials.gov Identifier:  NCT00073944
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-17