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

NCT02238496

Last updated date
Study Location
Columbia University Medical Center
New York, New York, 10032, United States
Contact
1-800-718-1021

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

1-800-718-1021

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Recurrent Brain Tumor, Glioblastoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Glioma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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

- 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

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- There is no limit on the number or type of prior chemotherapies except:


1. convection enhanced delivery, catheter based intra-tumoral treatment, or
carmustine (BCNU)/Gliadel® wafers


2. stereotactic radiosurgery, or re-irradiation of any type


3. agent designed to inhibit mTOR or PI3K/AKT


4. direct Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth
Factor Receptors (VEGFR) inhibitors


- Smoking or plan to smoke tobacco or marijuana during study therapy


- 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

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

pfizer-logoClinical Trials
Interested in learning more about clinical trials?
Discover how clinical trials work and the impact your participation could have.

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Recurrent Brain Tumor, Glioblastoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed GliomaPerifosine and Torisel (Temsirolimus) for Recurrent/Progressive Malignant Gliomas
NCT02238496
  1. New York, New York
  2. New York, New York
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Perifosine and Torisel (Temsirolimus) for Recurrent/Progressive Malignant Gliomas
Official Title  ICMJE Pilot Trial of Temsirolimus and Perifosine in Recurrent/Progressive Malignant Gliomas
Brief 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. 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
No Masking
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumor, Recurrent
  • Glioblastoma
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Mixed Glioma
Intervention  ICMJE
  • Procedure: Cytoreductive surgery
    Standard of care/routine cytoreductive glioma resection surgery. Arm B only.
    Other Name: Resection
  • Drug: Perifosine
    Perifosine is a pill that has not been approved by the FDA which blocks a messenger that tells cancer cells to grow.
    Other Names:
    • AEZS-104/D-21266
    • KRX-0401
  • Drug: Temsirolimus
    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.
    Other Name: Torisel
Study Arms  ICMJE
  • Surgical Cohort - cytoreductive surgery
    Cytoreductive 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).
    Interventions:
    • Procedure: Cytoreductive surgery
    • Drug: Perifosine
    • Drug: Temsirolimus
  • Medical Cohort - no cytoreductive surgery
    No-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).
    Interventions:
    • Drug: Perifosine
    • Drug: Temsirolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 7, 2016)
10
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2014)
17
Estimated Study Completion Date  ICMJE August 2022
Actual Primary Completion Date October 27, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • There is no limit on the number or type of prior chemotherapies except:

    1. convection enhanced delivery, catheter based intra-tumoral treatment, or carmustine (BCNU)/Gliadel® wafers
    2. stereotactic radiosurgery, or re-irradiation of any type
    3. agent designed to inhibit mTOR or PI3K/AKT
    4. direct Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitors
  • Smoking or plan to smoke tobacco or marijuana during study therapy
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02238496
Other Study ID Numbers  ICMJE AAAM3801
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Andrew B Lassman, MD, Columbia University
Study Sponsor  ICMJE Andrew B Lassman, MD
Collaborators  ICMJE
  • Pfizer
  • AEterna Zentaris
Investigators  ICMJE
Principal Investigator:Andrew B. Lassman, MDColumbia University
PRS Account Columbia University
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP