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The Purpose of This Study is to Test Any Good and Bad Effects of a Study Drug Called Abemaciclib (LY2835219) in Patients With Recurrent Brain Tumors.

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ClinicalTrials.gov Identifier: NCT03220646
Recruitment Status : Recruiting
First Posted : July 18, 2017
Last Update Posted : May 2, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to test any good and bad effects of a study drug called abemaciclib (LY2835219) in patients with recurrent brain tumors.

Condition or disease Intervention/treatment Phase
Brain Tumor Drug: abemaciclib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is an open-label, non-randomized, phase II trial of single-agent abemaciclib administered at previously defined MTD/RP2D in three cohorts of patients with primary brain tumors.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Abemaciclib in Patients With Recurrent Brain Tumors
Actual Study Start Date : July 13, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors
Drug Information available for: Abemaciclib

Arm Intervention/treatment
Experimental: A:recurrent IDH wildtype RB1 intact grade II and III gliomas
The main study cohort will consist of patients with recurrent IDH wildtype, RB1 wildtype, WHO grade II and III gliomas that have failed previous therapy.
Drug: abemaciclib
abemaciclib 200mg PO q12 hours (+/- 2 hours) on days 1-28 of each 28 day cycle.

Experimental: B:Recurrent glioma any grade
Ten patients who require standard of care cytoreductive surgery for recurrent astrocytoma, oligodendroglioma, or glioblastoma, will be offered pre-surgical abemaciclib and then resume the drug following recovery from surgery, continuing until disease progression or unacceptable toxicity analogous to the non-surgical patients in cohort A and C.
Drug: abemaciclib
200mg PO q12 hours (+/- 2 hours) for 4-7 days prior to surgery upon recovery from surgery, patients will resume abemaciclib at the same dose and schedule as cohorts A and C.

Experimental: C:All other recurrent brain tumors
This is an exploratory cohort including patients with recurrent IDH mutant glioma, meningioma, recurrent ependymoma, and recurrent PCNSL,and other primary brain tumors.
Drug: abemaciclib
abemaciclib 200mg PO q12 hours (+/- 2 hours) on days 1-28 of each 28 day cycle.




Primary Outcome Measures :
  1. radiographic response rate [ Time Frame: 6 months ]
    MRI (or CT) scan by RANO criteria.

  2. progression free survival (PFS) [ Time Frame: 6 months ]
    will be estimated by the Kaplan Meier method



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:

Cohort A specific inclusion:

  • Histologically confirmed IDHwt, RB intact, grade II or III glioma that has recurred after first line therapy (consisting of at least maximum feasible surgical resection and radiation therapy). There is no limit on the number of prior therapies or types of therapies patients can have received.
  • Measurable disease on imaging (1cm) or measurable non-enhancing tumor.
  • At least 12 weeks elapsed since prior radiotherapy

Cohort B specific inclusion:

  • Patients with histologically confirmed glioma of any grade (II-IV) who are planned for a standard of care surgical debulking/resection and for whom participation in this study would not cause a medically unacceptable delay in surgery.
  • Patients must have relapsed/progressed following therapy (consisting of at least maximum feasible surgical resection and radiation therapy).

Cohort C specific Inclusion:

  • Histologically confirmed IDH mutant glioma, meningioma, schwanomma, PCNSL, ependymoma, or other Primary Brain Tumors that have recurred despite previous standard of care therapy. Because this cohort is, in part, meant to allow patients access to therapy who might not otherwise be eligible for other clinical trials - deviations from standard of care treatment can be presented to and approved by the Principal Investigator for inclusion in the study.
  • Histologically confirmed PCNSL that has recurred after prior methotrexate-based chemotherapy or for whom methotrexate-based chemotherapy is deemed medically not in the patient's best interest.

Glioma patients:

  • Standard of care next generation sequencing via a CLIA certified platform must be available, or planned and at a minimum include IDH, and RB status.

All cohorts:

  • Patients must provide written informed consent prior to any screening procedures.
  • Age 18 years or older.
  • KPS ≥ 60
  • Willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • Patient is able to swallow and retain oral medication
  • Required baseline laboratory status:

    • Hemoglobin > 8 g/dL (SI Units: 80 g/L). Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
    • Platelet count ≥ 100 x 10^9/L
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without growth factor support
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
    • AST/SGOT and/or ALT/SGPT ≤ 3 x ULN
    • Serum Creatinine ≤ 1.5 x ULN
  • Stable dose of corticosteroids for > 5 days prior to baseline MRI
  • Before starting study treatment, patients must have recovered from toxic effects of prior therapies (except for residual alopecia or Grade 2 peripheral neuropathy) and at least 3 weeks must have elapsed since any prior signaling pathway modulators, (e.g., EGFR, FGFR, or other tyrosine kinase inhibitors), at least 3 weeks must have elapsed since temozolomide, 4 weeks must have elapsed since carboplatin or cisplatin, and at least 6 weeks from nitrosoureas (e.g., BCNU, CCNU). In general, at least 4 weeks must have elapsed from any other anticancer drug therapy (e.g. bevacizumab).
  • Patients must be able to undergo contrast enhanced MRI scans (or contrast enhanced CT scans for patients unable to tolerate MRI).
  • Patients must have shown unequivocal evidence for tumor progression by MRI (or CT for patients who cannot tolerate MRI) in comparison to a prior scan. The same type of scan, i.e., MRI (or CT for patients who cannot undergo MRI) must be used throughout the period of protocol treatment for tumor measurement.
  • Life expectancy of greater than 8 weeks
  • If a female of childbearing potential, must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of abemaciclib. If a male, agree to use a reliable method of birth control and to not donate sperm during the treatment period and for at least 3 months following the last dose of abemaciclib. Contraceptive methods may include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection.

Note: Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are collected for regulatory reporting and drug safety evaluation.

  • Women must agree not to breast feed while on abemaciclib treatment and for at least three months following the last dose of study therapy.

Exclusion Criteria:

  • No limit on number of prior therapies
  • Evidence of significant intracranial hemorrhage
  • No other investigational or standard anti-tumor therapy allowed
  • Patients must not have a known history of allergic reactions attributed to compounds of similar chemical or biologic composition.
  • Patients must not have a serious preexisting medical condition(s) or uncontrolled intercurrent illness that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea) or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients who have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological original (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. This applies only to patients who have a documented history of HIV; HIV testing is not otherwise required.
  • Have an active systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies)
  • Patients must not be on EIAEDs
  • Females who are pregnant or lactating
  • Must abstain from grapefruit juice
  • Patients must not have other active concurrent malignancy
  • Concurrent treatment on another clinical trial. Supportive care trials or non-therapeutic trials (i.e. Quality of life) are allowed.

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): NCT03220646


Contacts
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Contact: Thomas Kaley, MD 212-639-5122 kaleyt@mskcc.org
Contact: Ingo Mellinghoff, MD 646-888-2766

Locations
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United States, Connecticut
Hartford Healthcare Cancer Institute @ Hartford Hospital Recruiting
Hartford, Connecticut, United States, 06102
Contact: Ahmad Daher, MD    860-696-5169      
United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Thomas Kaley, MD    212-639-5122      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Thomas Kaley, MD    212-639-5122      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Thomas Kaley, MD    212-639-5122      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Thomas Kaley, MD    212-639-5122      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Thomas Kaley, MD    212-639-5122      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Thomas Kaley, MD    212-639-5122      
Contact: Ingo Mellinghoff, MD    646-888-2766      
Principal Investigator: Thomas Kaley, MD         
United States, Pennsylvania
Lehigh Valley Health Network Recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Tara Morrison, MD    610-402-7880      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Eli Lilly and Company
Investigators
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Principal Investigator: Thomas Kaley, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03220646     History of Changes
Other Study ID Numbers: 17-261
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: May 2, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Abemaciclib (LY2835219)
meningioma
Astrocytoma
ependymoma
Oligodendroglioma
CNS lymphoma
17-261
Additional relevant MeSH terms:
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Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases