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A Phase I Trial of Oral Perifosine With Different Loading Schedules in Patients With Refractory Neoplasms


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Trial of Oral Perifosine With Different Loading Schedules in Patients With Refractory Neoplasms


OBJECTIVES:

- Determine the dose-limiting toxicity and maximum tolerated dose of perifosine
administered as a varying series of loading and maintenance doses in patients with
refractory solid tumors, non-Hodgkin's lymphoma, chronic lymphocytic leukemia,
myelodysplastic syndromes, or Hodgkin's lymphoma.

- Determine the profile of adverse reactions (including changes in laboratory parameters)
in patients treated with this regimen.

- Determine any disease responses that may occur in patients treated with this regimen.

- Determine the steady-state pharmacology and pharmacokinetics of this regimen in these
patients.

OUTLINE: This is a dose-escalation study.

Patients receive a loading dose of oral perifosine on day 1 followed by a maintenance dose
2-3 times daily beginning on day 2 or 3 and continuing until day 21. Courses repeat every 28
days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating loading and maintenance doses of perifosine until
the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once
the MTD is determined, an additional 10 patients are treated at that dose level.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within 12-18
months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed solid tumor, non-Hodgkin's lymphoma, chronic lymphocytic
leukemia, myelodysplastic syndromes, or Hodgkin's lymphoma that has no effective
standard therapeutic option but requires systemic therapy

- No history of CNS neoplasms

- For prostate cancer:

- Tumor progression during blockade of testicular and adrenal androgens

- At least 4 weeks since prior flutamide or other antiandrogens without disease
improvement

- Leuprolide or other gonadotropin-releasing hormones should be maintained in
patients without an orchiectomy

- Testosterone in the castrate range

- For breast cancer:

- At least 4 weeks since any prior hormonal therapy with evidence of disease
progression

PATIENT CHARACTERISTICS:

Age:

- Over 18

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Platelet count greater than 50,000/mm^3

- Absolute granulocyte count greater than 500/mm^3

- Hemoglobin at least 9.0 g/dL

Hepatic:

- Bilirubin no greater than 1.5 mg/dL

- SGOT and SGPT no greater than 2.5 times normal

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance at least 60 mL/min

Cardiovascular:

- No history of unstable or newly diagnosed angina pectoris

- No myocardial infarction within the past 6 months

- No New York Heart Association class II-IV heart disease

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No recent acute or chronic gastrointestinal conditions (e.g., stomach ulcer or
enteritis) that might affect tolerability or drug absorption

- No allergic reaction to any medication with a structure similar to perifosine

- No pre-existing retinal disease or pathologic baseline electrooculogram

- No cataracts that would interfere with normal vision or require medical intervention

- No other serious concurrent illness that would preclude assessment of drug effect

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered

- At least 2 months since prior UCN-01

- More than 3 months since prior suramin

Endocrine therapy:

- See Disease Characteristics

- No concurrent corticosteroids except for physiological replacement or as antiemetics

Radiotherapy:

- At least 4 weeks since prior radiotherapy (6 weeks for bone-seeking radioisotopes)
and recovered

Surgery:

- See Disease Characteristics

Other:

- No other concurrent antineoplastic therapies

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Edward A. Sausville, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

CDR0000066960

NCT ID:

NCT00019656

Start Date:

August 1999

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • Unspecified Adult Solid Tumor, Protocol Specific
  • stage IV chronic lymphocytic leukemia
  • refractory chronic lymphocytic leukemia
  • unspecified adult solid tumor, protocol specific
  • previously treated myelodysplastic syndromes
  • de novo myelodysplastic syndromes
  • 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
  • secondary myelodysplastic syndromes
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • chronic myelomonocytic leukemia
  • atypical chronic myeloid leukemia, BCR-ABL1 negative
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • stage IV marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182
NCI - Center for Cancer ResearchBethesda, Maryland  20892