Neoadjuvant Chemoimmunotherapy in Recurrent Glioblastoma

NCT ID: NCT05700955

Last Updated: 2023-01-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2025-01-31

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..

Detailed Description

Participants will undergo screening tests to determine if they are eligible to participate. This will involve a complete history and physical examination, vital signs, blood tests including complete blood count (CBC), and serum chemistry (CMP).

Participants will receive one cycle of Temozolomide and Pembrolizumab prior to removing recurrent tumor, followed by three weekly cycles of treatment until progression.

Conditions

Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

temozolomide

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 Outdated medicine or medicine no longer needed will be returned to the Brown Cancer Center pharmacy for disposal.

Group Type: EXPERIMENTAL

Pembrolizumab and Temozolomide

Intervention Type: DRUG

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

Pembrolizumab

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.

Group Type: EXPERIMENTAL

Pembrolizumab and Temozolomide

Intervention Type: DRUG

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

Interventions

Pembrolizumab and Temozolomide

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

Intervention Type: DRUG

Other Intervention Names

Pembro and Temodar

Eligibility Criteria

Inclusion Criteria

1. Histopathologically proven diagnosis of glioblastoma prior to registration, by pathology report;

2. The tumor must be confined to the supratentorial compartment

3. The tumor tissue block from the primary diagnosis must be available to be sent for pathology review, after registration.

4. History/physical examination within 7 days prior to registration

5. Karnofsky performance status ≥ 60 within 7 days prior to registration.

6. 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

7. The patient must have completed chemoradiation with Radiotherapy and Temozolomide of the primary tumor according to standard of care.

8. Patients must have received no more than 3 prior therapies for Recurrent High Grade Glioma.

9. Subjects must have the ability to understand and willingness to sign a written informed consent document.

10. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.

12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria

1. Previous use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy.

2. Prior invasive malignancy (except non-melanomatous skin cancer) within the previous three years

3. 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.

4. Patient must have < 1.5 cm midline shift pre-operative

5. History of severe hypersensitivity reaction to any monoclonal antibody including pembrolizumab.

6. Patients who cannot safely undergo MRI due to non-MRI compatible pacemaker, or other reason.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Donald Miller

Donald M. Miller, M.D., Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Donald Miller, MD

Role: PRINCIPAL_INVESTIGATOR

University of Louisville/James Graham Brown Cancer Ctr.

Locations

James Graham Brown Cancer Ctr.

Louisville, Kentucky, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Donald Miller, MD

Role: CONTACT

Donald.miller@louisville.edu

502-562-4370

Facility Contacts

Donald Miller, MD

Role: primary

Donald.miller@louisville.edu

502-562-4370

Other Identifiers

22.0676

Identifier Type: -

Identifier Source: org_study_id