Ph II Study of Perifosine Plus Gleevec for Patients With GIST

This study has been completed.
Sponsor:
Collaborator:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
AEterna Zentaris
ClinicalTrials.gov Identifier:
NCT00455559
First received: March 30, 2007
Last updated: February 14, 2014
Last verified: November 2011
  Purpose

This is a Phase II trial designed to determine the efficacy and safety of perifosine plus imatinib mesylate in patients with advanced GIST who develop progressive disease or recurrence while receiving imatinib mesylate.


Condition Intervention Phase
Gastrointestinal Stromal Tumors
Drug: Perifosine
Drug: Imatinib Mesylate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Perifosine Plus Imatinib Mesylate for Patients With Resistant Gastrointestinal Stromal Tumor

Resource links provided by NLM:


Further study details as provided by AEterna Zentaris:

Primary Outcome Measures:
  • To determine the efficacy and safety of perifosine plus imatinib mesylate in patients with advanced GIST who develop progressive disease or recurrence while receiving imatinib mesylate. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine whether inhibition of Akt phosphorylation correlates with survival, time to disease progression, or response rate in patients with advanced GIST treated with imatinib mesylate plus perifosine. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: August 2006
Study Completion Date: October 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Perifosine 100 mg/d x 28 days
Drug: Perifosine
All patients: Imatinib mesylate
Drug: Imatinib Mesylate
All patients: Imatinib mesylate
Experimental: 2
Perifosine 900 mg/d (300 mg tid) 1 x weekly
Drug: Perifosine
All patients: Imatinib mesylate
Drug: Imatinib Mesylate
All patients: Imatinib mesylate

Detailed Description:

This is a Phase II study of perifosine in combination with imatinib mesylate in patients with advanced GIST. Each cycle lasts 28 days. There will be two treatment arms. On both arms, patients will continue the dose of imatinib mesylate taken during the period of disease progression. Patients will be randomized to one either a weekly or a daily perifosine treatment regimen at the time of registration.

  Eligibility

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

Inclusion Criteria

  • Histologically confirmed diagnosis of Kit expressing advanced GIST. This includes patients with metastatic disease or with primary tumors that are considered inoperable.
  • Patients may have "limited" (some but not all tumor foci progressing that are not amenable to local therapy) or "generalized" (widespread growth of all tumor foci) progression after adequate therapy with imatinib mesylate. Patients must have progression of disease on imatinib mesylate (at any dose greater than or equal to 300 milligrams daily).
  • Patients must have documented measurable disease by CT scan (> 2 cm by conventional CT or > 1 cm by spiral CT). If a targeted lesion has been previously embolized or irradiated, there must be objective evidence of progression of the lesion per CT scan, post-embolization or in the radiated field.
  • Patients must be at least four weeks out and recovered from acute toxicities of prior therapy, including radiation, biotherapy, chemotherapy or embolization (with the exception of imatinib mesylate).
  • All patients must have progressive disease on imatinib defined as:

    • An increase in unidimensional tumor size of >10% and did not meet criteria for PR by CT density
    • Any new lesions, including new tumor nodules in a previously cystic tumor, while on imatinib therapy
  • Patients should have a performance status of 0 to 2 according to the ECOG criteria.
  • Patients must have adequate organ function, unless in the opinion of the treating investigator, the abnormality is related to tumor and the study chairman or medical monitor agree the abnormality is unlikely to affect the safety of perifosine use. Adequate organ and marrow function is described in the protocol.
  • Patients must be able to ingest oral medications or to obtain them through a gastrostomy tube.
  • Patients must have ability to understand and the willingness to sign a written informed consent document.
  • Patients must be at least 18 years of age

Exclusion Criteria

  • Presence of known symptomatic CNS metastases
  • Significant concurrent medical disease other than GIST, including:

    • New York Heart Association class III or IV cardiac problems (e.g., congestive heart failure, acute myocardial infarction within 2 months of study), uncontrolled chronic renal
    • liver disease
    • uncontrolled diabetes
    • uncontrolled seizure disorder
    • active uncontrolled infection
    • organ allografts
    • psychiatric illness/social situations that would limit compliance with study requirements
  • History of active secondary cancer, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 or more years.
  • Patients who are receiving any other investigational agents or devices.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine).
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with perifosine.
  • Female patients who are pregnant or lactating are ineligible. All females of childbearing potential must have a negative serum pregnancy test within 72 hours of treatment. Men and women of childbearing potential must agree to employ adequate contraception to prevent pregnancy while on therapy and for 4 weeks after the completion of treatment. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  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: NCT00455559

Sponsors and Collaborators
AEterna Zentaris
M.D. Anderson Cancer Center
Investigators
Study Chair: Jonathan Trent, MD, PhD M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: AEterna Zentaris
ClinicalTrials.gov Identifier: NCT00455559     History of Changes
Other Study ID Numbers: Perifosine 210
Study First Received: March 30, 2007
Last Updated: February 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AEterna Zentaris:
Resistant Gastrointestinal Stromal Tumor
GIST
Perifosine
Gleevec

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014