Perifosine in Treating Patients With Advanced Soft Tissue Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00064324
First received: July 8, 2003
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

Phase II trial to study the effectiveness of perifosine in treating patients who have advanced soft tissue sarcoma. Drugs used in chemotherapy such as perifosine use different ways to stop tumor cells from dividing so they stop growing or die.


Condition Intervention Phase
Recurrent Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Drug: perifosine
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Perifosine in Soft Tissue Sarcoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival time [ Time Frame: Time from regstration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier (Kaplan and Meier 1958) and Cox Proportional Hazards (Cox D. 1972) modeling.

  • Time to disease progression [ Time Frame: Time from registration to documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier (Kaplan and Meier 1958) and Cox Proportional Hazards (Cox D. 1972) modeling.

  • Duration of response [ Time Frame: Date at which the patient's objective status is first noted to be either a complete response (CR) or partial response (PR) to the date progression is documented, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Average change over time for PK variable(s) [ Time Frame: Days 1 and 15 of course 1 and day 1 of courses 2-6 ] [ Designated as safety issue: No ]
    Estimated and tested via appropriate methods (i.e. t-test or Wilcoxon tests).


Enrollment: 46
Study Start Date: June 2003
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive a loading dose of oral perifosine every 6 hours for a total of 4 doses on day 1 and once daily on days 2-28 of course 1 only. For all subsequent courses, patients receive oral perifosine once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: perifosine
Given orally
Other Names:
  • D21266
  • octadecylphosphopiperidine
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the 6-month progression-free rate in patients treated with perifosine and having advanced soft tissue sarcoma.

SECONDARY OBJECTIVES:

I. To evaluate survival and time to progression. II. To evaluate objective tumor response status and duration. III. To evaluate adverse event rates. IV. To evaluate patterns of treatment failure. V. To evaluate pharmacokinetics.

OUTLINE: This is a multicenter study.

Patients receive a loading dose of oral perifosine every 6 hours for a total of 4 doses on day 1 and once daily on days 2-28 of course 1 only. For all subsequent courses, patients receive oral perifosine once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 17-46 patients will be accrued for this study within 9-12 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed advanced soft tissue sarcoma
  • Measurable disease; measurable disease lesions that are being monitored for response and have been previously irradiated must have progressed > 25% since completion of radiation therapy
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • PLT >= 100,000/uL
  • Total bilirubin =< upper normal limit (UNL)
  • AST =< 2.5 x UNL
  • Creatinine =< UNL or calculated creatinine clearance >= 60 mL/min (i.e. using the Cockcroft-Gault or Jeliffe methods)
  • Life expectancy >= 12 weeks
  • ECOG performance status (PS) 0 or 1
  • Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent

Exclusion Criteria:

  • Any of the following as this regimen may be harmful to a developing fetus or nursing child:

    • Pregnant women
    • Breastfeeding women
    • Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
    • NOTE: Pregnant women are excluded from this study because perifosine is an alkylphospholipid with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with perifosine, breastfeeding should be discontinued if the mother is treated with perifosine
  • Any of the following:

    • >= 3 prior cytotoxic chemotherapy regimens for metastatic sarcoma
    • Chemotherapy =< 4 weeks prior to study entry
    • Nitrosoureas or mitomycin C =< 6 weeks prior to study entry
    • Radiotherapy =< 4 weeks prior to study entry
    • Immunotherapy =< 4 weeks prior to study entry
    • Biologic therapy =< 4 weeks prior to study entry
    • Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
  • Uncontrolled brain metastases; NOTE: these patients are excluded because of the poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; however, if brain metastasis are treated and controlled for > 8 weeks, the patient would be eligible for this study
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia despite appropriate therapy, or psychiatric illness/social situations that would limit compliance with study requirements
  • HIV-positive patients receiving combination anti-retroviral therapy; NOTE: these patients are excluded from the study because of possible pharmacokinetic interactions with perifosine; appropriate studies may be undertaken in patients receiving combination anti-retroviral therapy when indicated
  • Prior malignancy, except for the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • Adequately treated noninvasive carcinoma
    • Other invasive cancer from which the patient has been disease-free for 5 years
  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: NCT00064324

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Howard Bailey Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00064324     History of Changes
Other Study ID Numbers: NCI-2012-02798, MC0276, 5972, N01CM17104
Study First Received: July 8, 2003
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 16, 2014