Perifosine in Treating Patients With Refractory Solid Tumors or Hematologic Cancer

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00019656
First received: July 11, 2001
Last updated: May 14, 2011
Last verified: August 2004
  Purpose

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

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Trial of Oral Perifosine With Different Loading Schedules in Patients With Refractory Neoplasms

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: August 1999
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019656

Locations
United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Edward A. Sausville, MD, PhD National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
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
Study First Received: July 11, 2001
Last Updated: May 14, 2011
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on September 18, 2014