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

NCT04220892 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: JWCI-18-0702 (I3Y-US-I011)
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

High Grade Glioma

Keywords

Immunotherapy; Pembrolizumab; Pemetrexed; Abemaciclib; Cyclin-dependent kinase 4 (CDK4); Cyclin-dependent kinase 6 (CDK6); Folate antimetabolite

Outcome Measures

Primary Outcomes (1)

• Tumor response rates

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

  one year

Secondary Outcomes (5)

• Toxicity assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.

  one year

• Progression free survival (PFS)

  one year

• Overall survival (OS)

  four years

• Levels of immunotherapeutic agents in specimens

  approximately 3 months

• Change in gene signature of tumor tissue after treatment

  approximately 6 months to 2 years

Study Arms (2)

Pembrolizumab plus Pemetrexed

EXPERIMENTAL

Pembrolizumab plus Pemetrexed

Drug: Pembrolizumab; Drug: Pemetrexed

Pembrolizumab plus Abemaciclib

EXPERIMENTAL

Pembrolizumab plus Abemaciclib

Drug: Pembrolizumab; Drug: Abemaciclib

Interventions

Pembrolizumab DRUG

200 mg intravenous (IV) every 3 weeks

Also known as: Keytruda

Pembrolizumab plus Abemaciclib; Pembrolizumab plus Pemetrexed

Pemetrexed DRUG

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

Also known as: Alimta

Pembrolizumab plus Pemetrexed

Abemaciclib DRUG

150 mg twice a day, by mouth.

Also known as: Verzenio

Pembrolizumab plus Abemaciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant or their legal representative has the ability to provide informed consent.
• Participant has the willingness to comply with all study procedures and availability for the duration of the study.
• Participant is being evaluated for a potential, or known, diagnosis of high grade glioma.
• Note:Participant must have a diagnosis of high grade (WHO Grade III or IV) glioma following brain surgery to proceed with study treatment.
• Participant is a candidate for brain surgery.
• Participant is male or female, ≥ 18 years of age.
• Participant has a Karnofsky Performance Status ≥ 60%.
• Participant has adequate organ function:
• ANC at least 1.5 x 10\^9/L or greater.
• Platelets at least 100 x 10\^9/L or greater.
• Hemoglobin at least 8 g/dL or greater.
• Total bilirubin 1.5 x upper limit of normal (ULN) or lower.
• ALT and AST 3 x ULN or lower.
• Serum creatinine 1.5 x ULN or lower.
• Participant has the ability to interrupt nonsteroidal anti-inflammatory (NSAIDS) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Pemetrexed.

You may not qualify if:

• Participant has received prior anti-cancer treatment for high-grade glioma.
• Participant has a diagnosis of immunodeficiency or active autoimmune disease.
• Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg daily of dexamethasone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. This is assessed after surgery, prior to starting drug treatment.
• Participant has received a live vaccine within 28 days prior to the first dose of study agent. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g., FluMist®).
• Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention, including, but not limited to:
• Uncontrolled diabetes;
• Renal disease that requires dialysis;
• Pulmonary disorder requiring supplemental oxygen to keep saturation \>95% and the situation is not expected to resolve within 2 weeks;
• Severe dyspnea at rest or requiring oxygen therapy;
• Interstitial lung disease;
• History of major surgical resection involving the stomach or small bowel;
• Preexisting Crohn's disease;
• Ulcerative colitis;
• Uncontrolled vasculitis and/or disease with known vasculitis;
• Preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea;

Sponsors & Collaborators

• Jose Carrillo: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

pembrolizumab; Pemetrexed; abemaciclib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Jose A Carrillo, MD

  Saint John's Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Neurosciences

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: January 7, 2020
• Study Start: July 8, 2020
• Primary Completion: July 8, 2020
• Study Completion: July 8, 2020
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)