Gastrointestinal Stromal TumorsPhase 2NCT00455559
Ph II Study of Perifosine Plus Gleevec for Patients With GIST
A Phase 2 study testing Perifosine and Imatinib Mesylate in people with Gastrointestinal Stromal Tumors, run by AEterna Zentaris.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- Perifosine and Imatinib Mesylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Aug 2006to Oct 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
About this study
Official title: A Phase II Study of Perifosine Plus Imatinib Mesylate for Patients With Resistant Gastrointestinal Stromal Tumor
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.
Read the 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.
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- Perifosine, Imatinib Mesylate
- Keywords
- Resistant Gastrointestinal Stromal Tumor, GIST, Perifosine, Gleevec
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerifosineDrug
Also called D-21266, KRX-0401
Imatinib MesylateDrug
Also called Gleevec, STI-571
| Study group | Role | What they receive |
|---|---|---|
| Perifosine 100 mg/d + imatinib mesylate | Experimental | 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. Receives: Drug: Perifosine; Drug: Imatinib Mesylate |
| Perifosine 900 mg/d + imatinib mesylate | Experimental | 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. Receives: Drug: Perifosine; Drug: Imatinib Mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: Every 8 weeks
Secondary outcomes (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.
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.
Measured: Every 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2007 (estimated)
- Study startAug 2006
- Primary completionNov 2010
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- AEterna Zentaris
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- M.D. Anderson Cancer Center
- Responsible party
- Sponsor
- Investigators
- Jonathan Trent, MD, PhD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00455559
- Sponsor's protocol ID
- Perifosine 210
- Status last verified
- Nov 2011
- First submitted
- 30 Mar 2007
- Last updated
- 22 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 27, No 15S (May 20 Supplement), 2009: 10563
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Perifosine Plus Imatinib Mesylate for Patients With Resistant Gastrointestinal Stromal Tumor
- ClinicalTrials.gov ID
- NCT00455559
- Acronym / sponsor ID
- Perifosine 210
- Conditions
- Gastrointestinal Stromal Tumors
- Keywords
- Resistant Gastrointestinal Stromal Tumor, GIST, Perifosine, Gleevec
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- AEterna ZentarisIndustry (pharma, biotech, devices)
- Collaborators
- M.D. Anderson Cancer Center
- Study start
- Aug 2006
- Primary completion
- Nov 2010 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 3 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perifosine 100 mg/d + imatinib mesylate | Experimental | Drug: Perifosine, Drug: Imatinib MesylatePerifosine 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. |
| Perifosine 900 mg/d + imatinib mesylate | Experimental | Drug: Perifosine, Drug: Imatinib MesylatePerifosine 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (14 listed)
- Presence of known symptomatic CNS metastases
- Significant concurrent medical disease other than GIST, including:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PerifosineAlso: D-21266, KRX-0401 | Drug | Perifosine 100 mg/d + imatinib mesylate, Perifosine 900 mg/d + imatinib mesylate |
| Imatinib MesylateAlso: Gleevec, STI-571 | Drug | Perifosine 100 mg/d + imatinib mesylate, Perifosine 900 mg/d + imatinib mesylate |
Primary outcome
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2018.
- Results publicationJournal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 27, No 15S (May 20 Supplement), 2009: 10563
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Trent, MD, PhD study chair
M.D. Anderson Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Perifosine and Imatinib Mesylate in people with Gastrointestinal Stromal Tumors, run by AEterna Zentaris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00455559, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2018.