Ph II Study of Perifosine Plus Gleevec for Patients With GIST

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00455559
Recruitment Status : Completed
First Posted : April 3, 2007
Last Update Posted : February 21, 2018
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
AEterna Zentaris

Brief Summary:
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 or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: Perifosine Drug: Imatinib Mesylate Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Perifosine Plus Imatinib Mesylate for Patients With Resistant Gastrointestinal Stromal Tumor
Study Start Date : August 2006
Actual Primary Completion Date : November 2010
Actual Study Completion Date : October 2011

Arm Intervention/treatment
Experimental: Perifosine 100 mg/d + imatinib mesylate
Perifosine 100 mg/d x 28 days Oral daily dose of perifosine 100 mg and oral daily dose of imatinib mesylate (current dose at time of progression of disease [PD] without interruption). Both drugs will be taken on a continuous basis and should be taken with food. Each cycle will be defined as 28 days.
Drug: Perifosine
Other Names:
  • D-21266
  • KRX-0401
Drug: Imatinib Mesylate
Other Names:
  • Gleevec
  • STI-571
Experimental: Perifosine 900 mg/d + imatinib mesylate
Perifosine 900 mg/d (300 mg tid), 1 x weekly Oral once-weekly dose of perifosine 900 mg (300 mg tid) + oral daily dose of imatinib mesylate (current dose at time of PD without interruption). Perifosine will be taken on days 1, 8, 15, and 22 of a 28-day cycle. Both medications should be taken with food.
Drug: Perifosine
Other Names:
  • D-21266
  • KRX-0401
Drug: Imatinib Mesylate
Other Names:
  • Gleevec
  • STI-571

Primary Outcome Measures :
  1. 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 ]
    This is a two-arm Phase II trial to determine whether the experimental regimen is likely to provide a 20% response rate while controlling the toxicity rate at 15%. Response will be evaluated at 2 months from the start of therapy, and is defined using the Choi Criteria. Toxicity is defined as any of the following events: regimen-related death, grade 3 transaminitis, grade 3 gastrointestinal toxicity, or grade 4 fatigue or higher within the same 2-month time window.

Secondary Outcome Measures :
  1. 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 ]
    As perifosine inhibits activation of Akt and has an acceptable safety profile, this Phase II trial is designed to assess antitumor activity of perifosine in patients with advanced GIST who are refractory to or relapsed from imatinib mesylate.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00455559

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

Publications of Results:
Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 27, No 15S (May 20 Supplement), 2009: 10563

Responsible Party: AEterna Zentaris Identifier: NCT00455559     History of Changes
Other Study ID Numbers: Perifosine 210
First Posted: April 3, 2007    Key Record Dates
Last Update Posted: February 21, 2018
Last Verified: November 2011

Keywords provided by AEterna Zentaris:
Resistant Gastrointestinal Stromal Tumor

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