Pilot Study of Pembrolizumab Combined With Pemetrexed or Abemaciclib for High Grade Glioma
- Conditions
- High Grade Glioma
- Interventions
- Registration Number
- NCT04220892
- Lead Sponsor
- Jose Carrillo
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab plus Pemetrexed Pembrolizumab Pembrolizumab plus Pemetrexed Pembrolizumab plus Pemetrexed Pemetrexed Pembrolizumab plus Pemetrexed Pembrolizumab plus Abemaciclib Abemaciclib Pembrolizumab plus Abemaciclib Pembrolizumab plus Abemaciclib Pembrolizumab Pembrolizumab plus Abemaciclib
- Primary Outcome Measures
Name Time Method Tumor response rates one year Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.
- Secondary Outcome Measures
Name Time Method Toxicity assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03. one year Proportion of patients experiencing adverse events
Overall survival (OS) four years The duration of time from start of treatment to death.
Progression free survival (PFS) one year The duration of time from start of treatment until objective tumor progression or death.
Levels of immunotherapeutic agents in specimens approximately 3 months Immunotherapeutic drug levels in specimens.
Change in gene signature of tumor tissue after treatment approximately 6 months to 2 years Comparison of genetic analysis of tumor tissue collected before and after study treatment.
Trial Locations
- Locations (1)
John Wayne Cancer Institute
🇺🇸Santa Monica, California, United States