Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-15

Study Completion Date

2028-06-06

Brief Summary

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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.

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Detailed Description

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PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of pembrolizumab in combination with standard therapy (surgery, external beam radiation therapy and temozolomide \[TMZ\] chemotherapy) in patients with newly diagnosed glioblastoma multiforme (GBM). (Neoadjuvant \[Group 1\]) II. To assess the 18 month overall survival rate of pembrolizumab in combination with standard therapy (surgery, external beam radiation therapy and TMZ chemotherapy) in patients with newly diagnosed glioblastoma multiforme (GBM). (Adjuvant \[Group 2\])

SECONDARY OBJECTIVES:

I. To assess adverse events (AE) and toxicity profile of pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM.

II. To assess time to progression in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only) III. To assess progression-free survival in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only) IV. To assess time to treatment failure in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only)

CORRELATIVE RESEARCH OBJECTIVES:

I. To assess the tumor PD-1/PD-L1 expression and inflammatory microenvironment profile by comparing PD-1/PD-L1 expression and T lymphocyte/monocytic infiltrates before and after administration of pembrolizumab treatment. (Neoadjuvant only) II. To assess the peripheral immunophenotype profile and GBM-associated antigen-specific T cell responses before and after receiving pembrolizumab treatment in combination with standard therapy.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP 1:

NEOADJUVANT (CYCLE 1): Patients receive pembrolizumab intravenously (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 orally (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.

GROUP 2:

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.

After completion of study treatment, patients are followed up at 30 days, every 3 months until progressive disease, then every 6 months for up to 5 years.

Conditions

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Glioblastoma Gliosarcoma Supratentorial Glioblastoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1 (pembrolizumab, surgery, temozolomide, radiation)

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.

Group Type EXPERIMENTAL

External Beam Radiation Therapy

Intervention Type RADIATION

Undergo external beam radiation therapy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Temozolomide

Intervention Type DRUG

Given PO

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Group 2 (pembrolizumab, temozolomide, radiation therapy )

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.

Group Type EXPERIMENTAL

External Beam Radiation Therapy

Intervention Type RADIATION

Undergo external beam radiation therapy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Temozolomide

Intervention Type DRUG

Given PO

Interventions

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External Beam Radiation Therapy

Undergo external beam radiation therapy

Intervention Type RADIATION

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Radiation Therapy

Undergo radiation therapy

Intervention Type RADIATION

Temozolomide

Given PO

Intervention Type DRUG

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Other Intervention Names

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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 Keytruda Lambrolizumab MK-3475 SCH 900475 Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation 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

Eligibility Criteria

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Inclusion Criteria

* 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)
* Aspartate transaminase (AST) AND alanine transaminase (ALT) =\< 2.5 x ULN (obtained =\< 28 days prior to registration)
* Creatinine =\< 1.0 x ULN OR measured or calculated creatinine clearance (per institutional standard) must be \>= 60 ml/min (obtained =\< 28 days prior to registration)
* Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only (POCBP)

* NOTE: Serum or urine pregnancy test allowed; if urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* POCBP must be willing to use adequate contraception starting with first dose through 120 days after last dose
* Provide written informed consent
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

* Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
* Willing to provide tissue and blood samples for correlative research purposes

Exclusion Criteria

* 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)
* Known history of active TB (Bacillus tuberculosis)
* Received a live vaccine =\< 30 days prior to registration
* History of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Hypersensitivity to pembrolizumab or any of its excipients
* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
* Received or planning to receive Optune device

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No