Neoplasms

All Conditions

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

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Dexamethasone acetate

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Hydroxocobalamin

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Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Folic Acid Antagonists

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

900 mg/m\^2 IV every 3 weeks. Supportive medications of ibuprofen, folic acid, vitamin B12, and dexamethasone.

Abemaciclib

Jose A Carrillo, MD

The purpose of this study is to evaluate any preliminary evidence of anticancer activity of pembrolizumab combined with either pemetrexed or abemaciclib when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma.

Additional aims of the study are to:

* Find out the side effects (good and bad) of pembrolizumab combined with pemetrexed or abemaciclib;
* • Evaluate tumor characteristics by collecting brain tumor tissue samples.
* Measure the amount of pembrolizumab, pemetrexed, and/or abemaciclib that gets in the body by collecting blood and cerebrospinal fluid.
* Look at biomarkers (biochemical features that can be used to measure the progress of disease or the effects of a drug) in blood and cerebrospinal fluid if available.

This is a prospective, open-label, multi-arm exploratory study of pembrolizumab in combination with pemetrexed or abemaciclib for the treatment of adult patients with newly diagnosed high grade glioma. Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a suspected diagnosis of high grade glioma will be approached for participation in this study. Tumor tissue obtained from surgery will be used for histological diagnosis and clinical molecular profiling, and excess tumor tissue may be collected for potential correlative studies. A small sample of blood and cerebrospinal fluid (CSF) for research will also be collected.

Once a diagnosis of high grade glioma is confirmed, the patient will be allocated to either Treatment Arm 1 (pembrolizumab + pemetrexed), or Treatment Arm 2 (pembrolizumab + abemaciclib). Treatment will be started approximately 7-42 days following surgery once the patient has recovered from surgery. Routine clinical evaluations will be performed prior to treatment initiation and throughout treatment as clinically indicated. Radiographic brain imaging will be performed approximately 21-42 after treatment initiation and then routinely for medical management. Tumor response will be assessed according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) Working Group criteria.

Treatment may continue until the patient experiences unacceptable toxicity or clear disease progression. The determination of whether to stop treatment due to disease progression will be based on the investigator's evaluation of the patient's clinical and radiographic condition, taking into consideration the interpretation of localized inflammatory responses that can mimic radiographic features of tumor progress. Patients discontinuing treatment will be directed by their treating physician to either receive a different treatment regimen (e.g., standard radiation therapy with or without chemotherapy) or undergo a clinically-indicated cytoreductive surgery. If another treatment is started, clinical evaluations and response assessments will continue as clinically-indicated and blood and CSF will be collected after the first month, then every three months.

Pilot Study of Pembrolizumab Combined With Pemetrexed or Abemaciclib for High Grade Glioma

Pilot Study of Pembrolizumab Combined With Pemetrexed or Abemaciclib for the Treatment of Patients With High Grade Glioma

Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.

Proportion of patients experiencing adverse events

The duration of time from start of treatment until objective tumor progression or death.

The duration of time from start of treatment to death.

Immunotherapeutic drug levels in specimens.

Comparison of genetic analysis of tumor tissue collected before and after study treatment.

Eli Lilly and Company

Jose Carrillo

Associate Professor, Neurosciences

Spots Global Cancer Trial Database for folate antimetabolite