Perifosine in Treating Patients With Refractory Solid Tumors or Hematologic Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00019656

Collaborator

(none)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of perifosine in treating patients who have refractory solid tumors or hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Unspecified Adult Solid Tumor, Protocol Specific	Drug: perifosine	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 1999

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
2	NCI - Center for Cancer Research	Bethesda	Maryland	United States	20892