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Brain Tumor, RecurrentPhase 1NCT02238496

Perifosine and Torisel (Temsirolimus) for Recurrent/Progressive Malignant Gliomas

A Phase 1 study testing Cytoreductive surgery, Perifosine and Temsirolimus in people with Brain Tumor, Recurrent and Glioblastoma, run by Andrew B Lassman, MD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to test the effectiveness of a drug called temsirolimus in combination with a drug called perifosine in treating brain tumors that have continued to grow after previous treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cytoreductive surgery, Perifosine and Temsirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
2 sitesUnited States
Study dates
8 Dec 2014to 14 Feb 2021
Phase
Phase 1
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 intracranial glioblastoma (GBM), including sub variants
  • At least 15 unstained slides or at least 1 tissue blocks must be collected from at least one prior surgery.
  • Received prior radiotherapy and prior temozolomide as treatment for the malignant glioma
  • Recovered from toxic effects of prior therapies and at least 2 weeks must have elapsed since any prior signaling pathway modulators; in general, at least 4 weeks must have elapsed from any other anticancer therapy
  • Able to undergo contrast enhanced magnetic resonance imaging (MRI) scans or CT scans
  • Shown unequivocal evidence for contrast enhancing tumor progression by MRI or CT in comparison to a prior scan
Show all 29Show fewer
  • Age > or = 18 years
  • Karnofsky Performance Status > or = 70
  • Life expectancy of > 8 weeks
  • Normal organ and marrow function, adequate liver function, and adequate renal function before starting therapy
  • Platelet count of at least 100,000/mm3 on at least 2 consecutive blood draws at least 1 week apart with results stable or trending upward
  • Normal coagulation
  • Cholesterol level < or = 350 mg/dl and triglycerides level < or = 400 mg/dl
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
  • Women of childbearing potential must have a negative beta-human chorionic gonadotropin (B-hCG) pregnancy test documented within 7 days prior to treatment
  • Women must agree not to breast feed
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability to swallow tablets
  • Group A (medical) specific inclusion criteria:
  • Fulfill all of the general inclusion criteria
  • At least 3 months between any prior brain radiotherapy and initiation of study therapy
  • MRI/CT must demonstrate measurable enhancing tumor of at least 1cm squared in cross-sectional area to allow assessment of radiographic response
  • On stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI/CT
  • The baseline brain MRI/CT must be performed less than 15 days prior to initiation of study treatment. Otherwise it must be repeated
  • Group B (surgical) specific inclusion criteria:
  • Fulfill all of the general inclusion criteria
  • Have cytoreductive surgery as part of their routine care for recurrent tumor
  • Have cytoreductive surgery as part of their routine care for recurrent tumor
  • A brain MRI/CT must be performed less than 15 days prior to initiation of study treatment. Otherwise it must be repeated

Who cannot join

  • There is no limit on the number or type of prior chemotherapies except:
  • convection enhanced delivery, catheter based intra-tumoral treatment, or carmustine (BCNU)/Gliadel® wafers
  • stereotactic radiosurgery, or re-irradiation of any type
  • agent designed to inhibit mTOR or PI3K/AKT
  • direct Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitors
  • Smoking or plan to smoke tobacco or marijuana during study therapy
Show all 18Show fewer
  • Plan to eat grapefruit or drink grapefruit juice during study therapy
  • Receiving any other investigational agents concurrently with study treatment
  • Taking hepatic Enzyme Inducing Anti-Epileptic Drug (EIAED)
  • Taking medications that are inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) for at least two weeks prior to study treatment
  • Uncontrolled intercurrent illness
  • HIV-positive patients on combination antiretroviral therapy
  • Other active concurrent malignancy
  • History of gout which can be exacerbated by perifosine
  • Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus or perifosine
  • Therapeutic anticoagulation
  • History of hemorrhagic or ischemic stroke
  • Prior intratumoral bleeding must be evaluated with a non-contrast head CT to exclude acute blood prior to start of treatment

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Pilot Trial of Temsirolimus and Perifosine in Recurrent/Progressive Malignant Gliomas

The purpose of this study is to test the effectiveness of a drug called temsirolimus in combination with a drug called perifosine in treating brain tumors that have continued to grow after previous treatment. Temsirolimus is an intravenous drug approved by the FDA for treatment of other cancers (kidney cancer, certain types of lymphoma) but not for brain tumors. Perifosine is a pill that has not been approved by the FDA which blocks a messenger that tells cancer cells to grow. Research suggests that combined treatment with both drugs is better than either alone, and that it is reasonably safe.

Read the detailed description

Malignant gliomas are the most common primary brain tumors, and glioblastoma (GBM) is the most common subtype in adults, representing more than 50% of gliomas. Standard initial treatment for newly diagnosed GBM consists of maximal surgical resection followed by radiotherapy to the tumor bed and chemotherapy with an oral DNA alkylator, temozolomide. However, recurrence is nearly universal despite standard therapy. There is no standard treatment at recurrence. Median survival is about 15 months from diagnosis and 6 months from recurrence. Once patients develop tumor progression, conventional chemotherapy is generally ineffective.

Being tested
Cytoreductive surgery, Perifosine, Temsirolimus
Keywords
Glioblastoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Glioma, akt-Oncogene Protein, mTOR Protein, Glioma, Brain Neoplasms, Brain Tumor, Recurrent
Medical subject headings
Brain Neoplasms, Glioblastoma, Astrocytoma, Oligodendroglioma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cytoreductive surgeryProcedure or surgery

    Also called Resection

    Standard of care/routine cytoreductive glioma resection surgery. Arm B only.

  • PerifosineDrug

    Also called AEZS-104/D-21266, KRX-0401

    Perifosine is a pill that has not been approved by the FDA which blocks a messenger that tells cancer cells to grow.

  • TemsirolimusDrug

    Also called Torisel

    Temsirolimus is an intravenous drug approved by the FDA for treatment of other cancers (kidney cancer, certain types of lymphoma) but not for brain tumors.

Study groups in NCT02238496
Study groupRoleWhat they receive
Surgical Cohort - cytoreductive surgeryOtherCytoreductive surgery planned (surgical cohort). After post-operative standard evaluations, patients will resume therapy. After anti-emetic prophylaxis, patients will receive the first divided dose of the perifosine loading dose after recovery from surgery. Patients will be observed for at least 30 minutes to ensure there has been adequate anti-emetic prophylaxis, and then patients will receive temsirolimus administered over 30-60 minutes IV. The remaining divided doses of the perifosine loading dose will then be administered. Patients will then return weekly for infusion of temsirolimus over 30-60 minutes IV. Dosing will be continuous although for the purposes of evaluation, a cycle will be defined as 4 weeks (28 days).
Receives: Procedure: Cytoreductive surgery; Drug: Perifosine; Drug: Temsirolimus
Medical Cohort - no cytoreductive surgeryOtherNo-Cytoreductive surgery planned (medical cohort). After anti-emetic prophylaxis, patients will receive the first divided dose of the perifosine loading dose. Patients will be observed for at least 30 minutes to ensure there has been adequate anti-emetic prophylaxis, and then patients will receive temsirolimus administered over 30-60 minutes IV. The remaining divided doses of the perifosine loading dose will then be administered. Patients will then return weekly for infusion of temsirolimus over 30-60 minutes IV. Dosing will be continuous although for the purposes of evaluation, a cycle will be defined as 4 weeks (28 days).
Receives: Drug: Perifosine; Drug: Temsirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical Benefit Rate

    Clinical Benefit Rate is defined as the radiographic response rate plus 6-month progression-free survival (PFS) rate.

    Measured: Up to 6 months from the start of treatment

Secondary outcomes (1)

  1. Median Overall Survival Rate

    Overall survival will be calculated by using the interval between the date in which the first study drug administration took place (Arm A), and first day of study drug administration following surgery (Arm B), until the date of subject expiration.

    Measured: Up to 48 months from start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2014 (estimated)
  2. Study start8 Dec 2014
  3. Primary completion27 Oct 2017
  4. Study completion14 Feb 2021

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02238496
Sponsor's protocol ID
AAAM3801
Status last verified
May 2023
First submitted
29 Aug 2014
Last updated
25 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cytoreductive surgery, Perifosine and Temsirolimus in people with Brain Tumor, Recurrent and Glioblastoma, run by Andrew B Lassman, MD at 2 sites in United States.

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 29 inclusion and 18 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 25 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Clinical Benefit Rate (time frame: Up to 6 months from the start of treatment). 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 NCT02238496.

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 25 May 2023.

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