Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma

NCT05700955 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 22.0676
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to test the safety of Pembrolizumab and Temozolomide in treating recurrent glioblastoma and to characterize the effect of this treatment on the participants tumor and immune system..

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Treatment toxicity

  Quantification of the frequency of adverse events in patients treated with neoadjuvant Pembrolizumab and Temozolomide with gross total resection of recurrent glioblastoma.

  Change in frequency of adverse events prior to gross total resection or recurrent glioblastoma

Secondary Outcomes (3)

• Overall Survival

  Every 8 weeks for 24 months

• Neurologic function and quality of life

  Every 8 weeks for 24 months

• Treatment Toxicity

  Change in frequency of adverse events after gross total resection or recurrent glioblastoma

Study Arms (2)

temozolomide

EXPERIMENTAL

Participants will take Temozolomide pills at home at a dose determined by body weight. They will take the pills for five days every 3 weeks. It will be dispensed by the pharmacy and must be stored in a closed container at room temperature, away from heat, moisture, and direct light and kept from freezing. It will be kept out of the reach of children. Outdated medicine or medicine no longer needed will be returned to the Brown Cancer Center pharmacy for disposal.

Drug: Pembrolizumab and Temozolomide

Pembrolizumab

EXPERIMENTAL

Pembrolizumab will be administered at a dose of 200 mg as an IV infusion through a freely flowing IV. The diluted solution will be administered intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. Other drugs will not be co-administered through the same infusion line. Pembrolizumab doses will be repeated every three weeks.

Drug: Pembrolizumab and Temozolomide

Interventions

Pembrolizumab and Temozolomide DRUG

Characterize the safety and immunologic/genomic/metabolomic effects of neoadjuvant Pembrolizumab and Temozolomide in recurrent glioblastoma.

Also known as: Pembro and Temodar

Pembrolizumab; temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically proven diagnosis of glioblastoma prior to registration, by pathology report;
• The tumor must be confined to the supratentorial compartment
• The tumor tissue block from the primary diagnosis must be available to be sent for pathology review, after registration.
• History/physical examination within 7 days prior to registration
• Karnofsky performance status ≥ 60 within 7 days prior to registration.
• Adequate Organ Function Laboratory Values
• Absolute neutrophil count (ANC) ≥1,500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥9.0 g/gL or ≥5.6 mmol/L, without recent transfusion
• Creatine ≤1.7 x upper limit of normal (ULN) or Measure or Calculated creatinine clearance ≥ 60.0mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)
• Total bilirubin ≤ 1.5 x ULN or Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN for subjects with liver metastases
• The patient must have completed chemoradiation with Radiotherapy and Temozolomide of the primary tumor according to standard of care.
• Patients must have received no more than 3 prior therapies for Recurrent High Grade Glioma.
• Subjects must have the ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Previous use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.
• Prior invasive malignancy (except non-melanomatous skin cancer) within the previous three years
• Severe, active co-morbidity defined as follows:
• Transmural myocardial infarction or unstable angina within the last 6 months prior to registration
• History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
• Known history of Tuberculosis or acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Patients with active autoimmune disease or history of autoimmune disease that might recur, will be considered on an individual basis
• Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
• Is pregnant or breastfeeding
• Has received prior therapy with an anti-Programmed Death 1 (PD-1), anti- Programmed Death-ligand 1 (PD-L1), or anti- Programmed Death-ligand 1 (PD-L2) agent.
• Patient must have \< 1.5 cm midline shift pre-operative
• History of severe hypersensitivity reaction to any monoclonal antibody including pembrolizumab.
• Patients who cannot safely undergo MRI due to non-MRI compatible pacemaker, or other reason.

Sponsors & Collaborators

• University of Louisville: lead

Study Sites (1)

James Graham Brown Cancer Ctr.

Louisville, Kentucky, 40202, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

pembrolizumab; Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Donald Miller, MD

  University of Louisville/James Graham Brown Cancer Ctr.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donald Miller, MD

CONTACT

502-562-4370; Donald.miller@louisville.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Donald M. Miller, M.D., Ph.D.

Model Details: The experience with neoadjuvant immunotherapy has raised the possibility of utilizing surgical resection/immunotherapy as a combination treatment for patients with recurrent glioblastoma. There are several reasons that suggest that surgical resection will likely enhance the activity of immunotherapy in glioblastoma.This includes 1) direct impact on tumor cells; 2) impact on immune cells; and 3) impact on immune infiltration. The combination of the evidence that neoadjuvant Pembrolizumab has a positive effect on GBM survival, the evidence in lung cancer that chemotherapy and checkpoint inhibitor therapies are synergistic and the clinical utility of surgery in patients with recurrent glioblastoma has suggested that the neoadjuvant administration of Pembrolizumab and temozolomide prior to and following maximal surgical resection represents a very attractive experimental combination for the treatment of recurrent glioblastoma.

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: January 26, 2023
• Study Start: November 1, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: January 26, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)