Perifosine in Treating Patients With Refractory Solid Tumors or Hematologic Cancer

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Primary Purpose:	Treatment
Official Title:	A Phase I Trial of Oral Perifosine With Different Loading Schedules in Patients With Refractory Neoplasms
Study Start Date :	August 1999

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:	Edward A. Sausville, MD, PhD	National Cancer Institute (NCI)

More Information

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Publications of Results:

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.

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.

ClinicalTrials.gov Identifier:	NCT00019656 History of Changes
Obsolete Identifiers:	NCT00001799
Other Study ID Numbers:	CDR0000066960; NCI-99-C-0043; NCI-T98-0065
First Posted:	January 27, 2003
Last Update Posted:	April 29, 2015
Last Verified:	August 2004

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Lymphoma; Syndrome; Leukemia; Neoplasms; Myelodysplastic Syndromes; Preleukemia; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Neoplasms by Histologic Type	Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease; Pathologic Processes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions