Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma

NCT03197506 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC1572NCI-2017-0110616-002965
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies the side effects and how well pembrolizumab works in combination with standard therapy in treating patients with glioblastoma. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in the chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving pembrolizumab and standard therapy comprising of temozolomide and radiation therapy may kill tumor cells.

Conditions

Glioblastoma; Gliosarcoma; Supratentorial Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose Limiting Toxicities

  A dose limiting toxicity DLT will be defined as an adverse event attributed (definitely, probably, or possibly) to pembrolizumab per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Criteria: Grade 4 or higher neutropenia last at least 7 days. Grade 3 electrolyte alteration, nausea, vomiting, or diarrhea lasting at least 3 days. Grade 3 or higher neurologic toxicity. Toxicities leading to delayed treatment of at least 14 days. Inability to proceed to planned surgical resection. Inability to receive at least 75 percent of cumulative radiation dose.

  189 days

• Group 2 Overall Survival (OS) at 18 Months

  Defined as the number of patients who are alive up to 18 months after beginning study therapy.

  18 months

Secondary Outcomes (7)

• Incidence of Adverse Events

  14 months

• Time Until Treatment Related Grade 3+ Adverse Event

  14 months

• Time Until Any Treatment Related Adverse Event

  Up to 5 years

• Time Until Hematologic Nadirs

  Up to 5 years

• Time to Progression (Group 2)

  36 months

Study Arms (2)

Group 1 (pembrolizumab, surgery, temozolomide, radiation)

EXPERIMENTAL

NEOADJUVANT (CYCLE 1): Patients receive pembrolizumab IV over 30 minutes on day 1. SURGERY (CYCLE 2): Patients undergo standard of care surgery within days 4-7. CONCURRENT (CYCLE 3): Starting 21-35 days after surgery, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 8-54. Patients also undergo external beam radiation therapy every 5 days per week on days 8-54. ADJUVANT (CYCLE 4-8): Within 3-5 weeks after completing radiation therapy, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 1-5 every 28 days. Treatment repeats every 63 days for up to 5 cycles in the absence of disease progression or unexpected toxicity.

Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy; Drug: Temozolomide; Procedure: Therapeutic Conventional Surgery

Group 2 (pembrolizumab, temozolomide, radiation therapy )

EXPERIMENTAL

CONCURRENT (CYCLE 1): Starting 21-35 days after surgery, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 8-54. Patients also undergo external beam radiation therapy every 5 days per week on days 8-54. ADJUVANT (CYCLES 2-6): Within 3-5 weeks after completing radiation therapy, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 of cycles 2-5 and 1 and 22 of cycle 6 (up to a total of 17 doses). Patients also receive temozolomide PO daily on days 1-5, 29-33, and 57-61 of cycles 2 and 6, days 22-26 and 50-54 of cycle 3, days 15-19 and 43-47 of cycle 4, days 8-12 and 36-40 of cycle 5. Treatment repeats every 63 days for up to 5 cycles in the absence of disease progression or unexpected toxicity.

Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy; Drug: Temozolomide

Interventions

External Beam Radiation Therapy RADIATION

Undergo external beam radiation therapy

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Group 1 (pembrolizumab, surgery, temozolomide, radiation); Group 2 (pembrolizumab, temozolomide, radiation therapy )

Laboratory Biomarker Analysis OTHER

Correlative studies

Group 1 (pembrolizumab, surgery, temozolomide, radiation); Group 2 (pembrolizumab, temozolomide, radiation therapy )

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Group 1 (pembrolizumab, surgery, temozolomide, radiation); Group 2 (pembrolizumab, temozolomide, radiation therapy )

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Group 1 (pembrolizumab, surgery, temozolomide, radiation); Group 2 (pembrolizumab, temozolomide, radiation therapy )

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Group 1 (pembrolizumab, surgery, temozolomide, radiation); Group 2 (pembrolizumab, temozolomide, radiation therapy )

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Group 1 (pembrolizumab, surgery, temozolomide, radiation)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Histological confirmation of supratentorial glioblastoma (also known as astrocytoma grade IV, gliosarcoma)
• NOTE: Grade IV IDH-mutant astrocytoma is also allowed
• Neoadjuvant patients only: Have an enhancing mass on magnetic resonance imaging (MRI) amenable to \> 90% resection of contrast-enhancing tumor (as determined by the neurosurgeon pre-operatively) and histological diagnosis of glioblastoma or astrocytoma from a prior biopsy or surgery
• NOTE: Biopsy or subtotal resection must have been =\< 43 days prior to registration
• Neoadjuvant patients only: Willing to undergo craniotomy and resection of their brain tumor at Mayo Clinic in Rochester, Minnesota (MN)
• Adjuvant patients only: Must have undergone craniotomy and resection of their brain tumor =\< 6 weeks prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 28 days prior to registration)
• Platelet count \>= 100,000/mm\^3 (obtained =\< 28 days prior to registration)
• Hemoglobin \>= 9.0 g/dL without transfusion or erythropoietin (EPO) dependency (=\< 7 days prior to assessment) (obtained =\< 28 days prior to registration)
• Prothrombin time (PT) =\< 1.5 x upper limit of normal (ULN) unless patient is receiving anticoagulant therapy and PT or partial prothrombin time (PTT) is within therapeutic range of intended use of coagulants (obtained =\< 28 days prior to registration)
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =\< 28 days prior to registration)
• Albumin \>= 2.5 mg/dL (obtained =\< 28 days prior to registration)
• Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN (obtained =\< 28 days prior to registration)

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Neoadjuvant patients only: Signs or symptoms of life-threatening raised intracranial pressure: as defined by the treating neurosurgeon, including severe headache, nausea, decreasing level of consciousness, precluding 4-7 day delay in scheduling neurosurgery
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Other active malignancy =\< 5 years prior to registration
• EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
• NOTE: If there is a history or prior malignancy, the patient must not be receiving other specific treatment for their cancer
• History of myocardial infarction =\< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs; NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Radiation; pembrolizumab; Radiotherapy; 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)

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

Results Point of Contact

• Title: Ian Parney
• Organization: Mayo Clinic

parney.ian@mayo.edu

507-255-3199

Study Officials

• Ian F. Parney, MD, PhD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: June 23, 2017
• Study Start: January 15, 2018
• Primary Completion: July 16, 2024
• Study Completion (Estimated): June 6, 2028
• Last Updated: March 25, 2026
• Results First Posted: March 25, 2026

Record last verified: 2026-03

Locations

US (3)