Nervous System Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Rare Diseases

Drug Resistant Epilepsy

Epilepsy

Glioma

Seizures

Epilepsies, Partial

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Diseases

Central Nervous System Diseases

Neurologic Manifestations

Neuroepithelioma

Anticonvulsants

All Drugs and Chemicals

Patients receive perampanel PO QD for 40 weeks in the absence of disease progression or unacceptable toxicity.

Patients receive ASD per standard of care for 40 weeks in the absence of disease progression or unacceptable toxicity.

Anticonvulsant Agent

Perampanel

Quality-of-Life Assessment

Questionnaire Administration

William Tatum

This phase IV trial studies the side effects and how well perampanel works in reducing seizure frequency in patients with high-grade glioma and focal epilepsy. Perampanel is a drug used to treat seizures. Giving perampanel together with other anti-seizure drugs may work better in reducing seizure frequency in patients with high-grade glioma and focal epilepsy compared to alternate anti-seizure drugs alone.

PRIMARY OBJECTIVE:

I. Demonstrate the efficacy and safety of perampanel (PER) on seizure frequency in adult patients with biopsy-proven high-grade glioma and focal epilepsy compared with alternate anti-seizure drugs (ASDs).

SECONDARY OBJECTIVES:

I. To assess the change in neurocognitive function and brain magnetic resonance imaging (MRI) progression over the course of PER treatment with a daily dose of 4 mg (up to -8mg) in patients with biopsy-proven high-grade glioma and focal epilepsy compared with alternate ASDs.

II. To identify a biomarker-specific response to seizure-reduction in patients treated with PER in patients with a biopsy-proven high-grade glioma (i.e., IDH-mutant versus \[vs\] wildtype).

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP A: Patients receive perampanel orally (PO) once daily (QD) for 40 weeks in the absence of disease progression or unacceptable toxicity.

GROUP B: Patients receive ASD per standard of care for 40 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 months.

Perampanel for the Reduction of Seizure Frequency in Patients With High-grade Glioma and Focal Epilepsy

A Phase IV, Prospective, Open-Label, Parallel Study Evaluating the Effect of an Adjunctive Anti-Seizure Medication Using a Glutamatergic Modulator in Patients With Focal Epilepsy and High-Grade Glioma

Will compare seizure frequency before and 3 months after treatment with monotherapy and adjunctive PER and use descriptive statistics to demonstrate differences in responders. A P-value \< 0.05 will be used to reflect statistical significance.

Will compare seizure frequency before and 6 months after treatment with monotherapy and adjunctive PER and use descriptive statistics to demonstrate differences in responders. A P-value \< 0.05 will be used to reflect statistical significance.

Chi-square and Student T-test will be used to measure differences in assessment and change during the study period.

Mayo Clinic

Principal Investigator

Patients receive perampanel PO QD for 40 weeks in the absence of disease progression or unacceptable toxicity.

Perampanel: Given PO

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Arm A (Perampanel)

Patients receive ASD per standard of care for 40 weeks in the absence of disease progression or unacceptable toxicity.

Anticonvulsant Agent: Given ASD

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Arm B (ASD)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Study was terminated due to the funding sponsor(EISAI) sold the US rights to the medication and can no longer provide it to patients for the study.

William Tatum, D.O.

1 participant was randomized to Arm B, but did not complete the 3 month follow-up due to study termination. In Arm A, only 2 participants met the study 3 month mark prior to study termination.

Number of Patients With a High-grade Glioma Who Achieve a > 50% Reduction in Focal Seizures With Perampanel (PER) 4 mg Daily After Failing 1 or More Anti-seizure Drugs (ASDs)

1 participant was randomized to Arm B, but did not complete the 6 month follow-up due to study termination. In Arm A, only 1 participant met the study 6 month mark prior to study termination.

Number of Patients With a High-grade Glioma Who Achieve a > 50% Reduction in Focal Seizures With PER 4 mg Daily After Failing 1 or More ASDs

1 participant was randomized to Arm B, but did not receive PER treatment. In Arm A, only 2 participants met the study 3 month mark prior to study termination.

Number of Participants Alive at 3 Months With High-grade Glioma Treated With PER

The study was terminated due to the funding sponsor no longer being able to provide study medication. Data for this outcome measure was not collected nor analyzed.

Decline in Neuropsychological Function

Overall Study

Recurrence

Cholangiocarcinoma

Glioblastoma

Disease Attributes

Astrocytoma

Adenocarcinoma

Carcinoma

Bile Duct Cancer

Antineoplastic Agents

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI, as well as a tumor biopsy and blood sample collection on study.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Patricia M LoRusso

This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that has spread from where it first started (primary site) to other places in the body (metastatic) and that does not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To estimate the overall response rates of olaparib in subjects with recurrent/progressive IDH1/2-mutant solid tumors, who will be recruited to 3 cohorts: a. glioma, b. cholangiocarcinoma, c. other solid malignant tumors.

SECONDARY OBJECTIVES:

I. To estimate the distribution of progression free survival (PFS) of olaparib in adults with recurrent/progressive IDH1/2-mutant glioma and cholangiocarcinoma.

II. To estimate the overall survival (OS) in adults with recurrent/progressive IDH1/2- mutant glioma and cholangiocarcinoma.

III. To determine the duration of response in adults with recurrent/progressive IDH1/2-mutant glioma, cholangiocarcinoma or other solid malignant tumors.

IV. To confirm the safety and tolerability of olaparib monotherapy.

EXPLORATORY OBJECTIVES:

I. To describe 2HG concentration in plasma by mass spectrometry at baseline and at specific timepoints and correlate with treatment response.

II. To describe 2HG levels in tumor biopsies from prior to the beginning of treatment and at specific timepoints and correlate with treatment response.

III. To evaluate in tumor biopsies and in liquid biopsies performed at baseline and at specific timepoints if co-occurring alterations detected via multiplexed immunofluorescence, mass cytometry (CyTOF)-imaging mass cytometry (IMC), ribonucleic acid (RNA) sequencing and/or deoxyribonucleic acid (DNA) sequencing can be associated with differential levels of 2HG production, treatment response and resistance.

OUTLINE:

Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a computer tomography (CT) scan and/or magnetic resonance imaging (MRI), as well as a tumor biopsy and blood sample collection on study.

After completion of study treatment, patients are followed up for 30 days.

Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations

A Phase 2 Study of the PARP Inhibitor Olaparib (AZD2281) in IDH1 and IDH2 Mutant Advanced Solid Tumors

Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically versus (vs.) time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Will be detected via mass cytometry, ribonucleic acid sequencing and/or deoxyribonucleic acid sequencing. Will be associated with differential levels of 2HG production, treatment response and resistance. Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Will be determined by investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1 for extracranial solid tumors, Response Assessment in Neuro-Oncology criteria for intracranial glioma. Overall response rate and a 90% creditable interval in each cohort will be estimated using the approach described by Koyama. For the other solid tumors cohort, descriptive statistics and graphical displays will be used to summarize results within tumor types.

For time to event endpoints, Kaplan-Meier curves will be used to demonstrate distributions and median estimates will be reported with 95% confidence intervals. For each cohort, graphical displays such as swimmer plots, will be used to demonstrate patterns of response, progression and death, and in the third cohort they will also indicate disease type.

Adverse events will be tabulated by type and grade in each cohort, and also across cohorts.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Perampanel for the Reduction of Seizure Frequency in Patients With High-grade Glioma and Focal Epilepsy	NCT04650204	Intractable Epi... Malignant Gliom... Seizure Disorde... WHO Grade 2 Gli... WHO Grade 3 Gli...	Anticonvulsant ... Perampanel Quality-of-Life... Questionnaire A...	18 Years -	Mayo Clinic
Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations	NCT03212274	Advanced Malign... Glioblastoma Recurrent Chola... Recurrent Gliom... Recurrent Malig... WHO Grade 2 Gli... WHO Grade 3 Gli...	Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Olaparib	18 Years -	National Cancer Institute (NCI)
Perampanel for the Reduction of Seizure Frequency in Patients With High-grade Glioma and Focal Epilepsy	NCT04650204	Intractable Epi... Malignant Gliom... Seizure Disorde... WHO Grade 2 Gli... WHO Grade 3 Gli...	Anticonvulsant ... Perampanel Quality-of-Life... Questionnaire A...	18 Years -	Mayo Clinic
Perampanel for the Reduction of Seizure Frequency in Patients With High-grade Glioma and Focal Epilepsy	NCT04650204	Intractable Epi... Malignant Gliom... Seizure Disorde... WHO Grade 2 Gli... WHO Grade 3 Gli...	Anticonvulsant ... Perampanel Quality-of-Life... Questionnaire A...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for who grade 2 glioma