Clinical trial NCT00073944: BCX-1777 in Treating Patients With Refractory Cancer
Official title: Phase I Pharmacology Study Of Oral And Intravenous BCX-1777 In Patients With Refractory T-Cell And Non-T-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-12-11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
Study officials:
affiliation: Inveresk Research Group, Incorporated
name: Alex Shalaurov, MD, PhD
role: STUDY_CHAIR
References: