Perifosine in Treating Patients With Refractory Solid Tumors or Hematologic Cancer

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00019656
• Other study ID #: CDR0000066960
• Secondary ID: NCI-99-C-0043NCI
• Status: Completed
• Phase: Phase 1
• First received: July 11, 2001
• Last updated: April 28, 2015
• Start date: August 1999

Study information

• Verified date: August 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00001799

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Neoplasms
• Preleukemia
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• perifosine

Locations

Country	Name	City	State
United States	NCI - Center for Cancer Research	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Messmann RA, Headlee D, Woo EW, et al.: A phase I trial of oral perifosine with different loading and maintenance schedules in patients with refractory neoplasms. [Abstract] Proc Am Assoc Cancer Res 42: A-2880, 2001.

Monga M, Messmann RA, Headlee D, et al.: A phase I trial of oral perifosine in patients with refractory neoplasms. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1837, 7b, 2002.