BCX-1777 in Treating Patients With Refractory Cancer

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