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Trial record 28 of 228 for:    "Anaplastic oligodendroglioma"

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

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ClinicalTrials.gov Identifier: NCT02238496
Recruitment Status : Unknown
Verified September 2016 by Andrew Lassman, Columbia University.
Recruitment status was:  Active, not recruiting
First Posted : September 12, 2014
Last Update Posted : September 8, 2016
Sponsor:
Collaborators:
Pfizer
AEterna Zentaris
Information provided by (Responsible Party):
Andrew Lassman, Columbia University

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.

Condition or disease Intervention/treatment Phase
Brain Tumor, Recurrent Glioblastoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Mixed Glioma Procedure: Cytoreductive surgery Drug: Perifosine Drug: Temsirolimus Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Trial of Temsirolimus and Perifosine in Recurrent/Progressive Malignant Gliomas
Study Start Date : July 2014
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016


Arm Intervention/treatment
ARM B
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).
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

ARM A
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).
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




Primary Outcome Measures :
  1. Change in tumor size [ Time Frame: Every 8 weeks, starting at 8 weeks after Day 1 of treatment, and up to 48 months ]
    Tumor measurements will be calculated and compared to baseline measurements to determine if the regimen induces radiographic response (tumor shrinkage or stabilization) and/or delay in disease progression. These statuses will be categorized as Complete Response (CR), Partial Response (PR), Minor Response (MR), Stable Disease (SD), Progressive Disease (PD), and Unknown (UNK).


Secondary Outcome Measures :
  1. Change in tumor size specifically at 6 months [ Time Frame: Up to 6 months from drug administration ]
    Subjects' disease status will be evaluated for progression at 6 months: 6 months from first day of study drug administration (Arm A) and 6 months from first day of study drug administration following surgery (Arm B). This will be accomplished via radiographic measurement comparisons between follow-up on-study scans, compared to the baseline scan tumor measurements.

  2. Median Overall Survival Rate [ Time Frame: From time of first study drug administration until expiration, (approximately 48 months) ]
    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.



Information from the National Library of Medicine

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

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

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 ClinicalTrials.gov identifier (NCT number): NCT02238496


Locations
United States, New York
Columbia University Medical Center
New York City, New York, United States, 10032
Memorial Sloan-Kettering Cancer Center
New York City, New York, United States, 10065
Sponsors and Collaborators
Andrew Lassman
Pfizer
AEterna Zentaris
Investigators
Principal Investigator: Andrew B Lassman, MD Columbia University

Additional Information:
Responsible Party: Andrew Lassman, John Harris Associate Professor of Neurology, Columbia University
ClinicalTrials.gov Identifier: NCT02238496     History of Changes
Other Study ID Numbers: AAAM3801
First Posted: September 12, 2014    Key Record Dates
Last Update Posted: September 8, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Andrew Lassman, Columbia University:
Glioblastoma
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Mixed Glioma
akt-Oncogene Protein
mTOR Protein
Glioma
Brain Neoplasms
Brain Tumor, Recurrent

Additional relevant MeSH terms:
Glioblastoma
Glioma
Brain Neoplasms
Astrocytoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents