GlioblastomaPhase 2NCT03197506
Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma
A Phase 2 study testing External Beam Radiation Therapy, Laboratory Biomarker Analysis and Pembrolizumab in people with Glioblastoma and Gliosarcoma, run by Mayo Clinic at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma, Supratentorial Glioblastoma
- What is being tested?
- External Beam Radiation Therapy, Laboratory Biomarker Analysis and Pembrolizumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Jan 2018to 6 Jun 2028
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: Phase II Study of Pembrolizumab (MK-3475) in Combination With Standard Therapy for Newly Diagnosed Glioblastoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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
- Glioblastoma, Gliosarcoma, Supratentorial Glioblastoma
- Being tested
- External Beam Radiation Therapy, Laboratory Biomarker Analysis, Pembrolizumab, Radiation Therapy, Temozolomide
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
External Beam Radiation TherapyRadiation
Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy
Undergo external beam radiation therapy
Laboratory Biomarker AnalysisOther
Correlative studies
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
Radiation TherapyRadiation
Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated
Undergo radiation therapy
TemozolomideDrug
Also called 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
Given PO
Therapeutic Conventional SurgeryProcedure or surgery
Undergo surgery
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 18 months
Secondary outcomes (5)
Incidence of Adverse Events
The overall count of participants that reported Grade 3 or higher adverse events considered at least possibly related to treatment will be calculated and reported in this section. The number of all adverse events will be tabulated and summarized in the adverse events section of this report. Group 1 dose levels are combined due to scientific interest being in the comparison of group 1, the neoadjuvant group, to group 2, the adjuvant group. Per protocol this exploratory and hypothesis generating endpoint may be analyzed by group. All patients that received the same dose level of treatment are combined to better show the adverse events encountered by the treatment population.
Measured: 14 months
Time Until Treatment Related Grade 3+ Adverse Event
Defined as the time from treatment start date to the date of the patients first grade 3 or higher event deemed related to treatment. Group 1 dose levels are combined due to scientific interest being in the comparison of group 1, the neoadjuvant group, to group 2, the adjuvant group. Per protocol this exploratory and hypothesis generating endpoint may be analyzed by group. All patients that received the same dose level of treatment are combined to better show the adverse events encountered by the treatment population.
Measured: 14 months
Time to Progression (Group 2)
Defined as the time from start of study treatment to disease progression. Will be assessed using the immunotherapy response assessment for neuro-oncology (iRANO) criteria.
Measured: 36 months
Progression-free Survival (Group 2)
Defined as the time from starting study treatment to the date of disease progression or death resulting from any cause, whichever comes first. Will be assessed according to iRANO criteria.
Measured: 36 months
Time to Treatment Failure (Group 2)
Defined as the time from beginning study therapy to documentation of disease progression, unacceptable adverse event(s), or refusal to continue participation by the patient.
Measured: 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2017
- Study start15 Jan 2018
- Primary completion16 Jul 2024
- Study completion6 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ian F. Parney, MD, PhD, Principal investigator, Mayo Clinic in Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03197506
- Sponsor's protocol ID
- MC1572
- Other IDs
- NCI-2017-01106, MC1572, 16-002965
- Status last verified
- Aug 2026
- First submitted
- 21 Jun 2017
- Last updated
- 22 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Pembrolizumab (MK-3475) in Combination With Standard Therapy for Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT03197506
- Acronym / sponsor ID
- MC1572
- Conditions
- Glioblastoma, Gliosarcoma, Supratentorial Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 16 Jul 2024 (actual)
- Study completion
- 6 Jun 2028 (estimated)
- First posted
- 23 Jun 2017 (actual)
- Results
- Posted 25 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 (pembrolizumab, surgery, temozolomide, radiation) | Experimental | Radiation: External Beam Radiation Therapy, Other: Laboratory Biomarker Analysis, Biological: Pembrolizumab, Radiation: Radiation Therapy, Drug: Temozolomide, Procedure: Therapeutic Conventional SurgeryNEOADJUVANT (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 2 (pembrolizumab, temozolomide, radiation therapy ) | Experimental | Radiation: External Beam Radiation Therapy, Other: Laboratory Biomarker Analysis, Biological: Pembrolizumab, Radiation: Radiation Therapy, Drug: TemozolomideCONCURRENT (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Age >= 18 years
- Histological confirmation of supratentorial glioblastoma (also known as astrocytoma grade IV, gliosarcoma)
- 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
- 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
Key exclusion criteria (21 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| External Beam Radiation TherapyAlso: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam RadiotherapyUndergo external beam radiation therapy | Radiation | Group 1 (pembrolizumab, surgery, temozolomide, radiation), Group 2 (pembrolizumab, temozolomide, radiation therapy ) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Group 1 (pembrolizumab, surgery, temozolomide, radiation), Group 2 (pembrolizumab, temozolomide, radiation therapy ) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Group 1 (pembrolizumab, surgery, temozolomide, radiation), Group 2 (pembrolizumab, temozolomide, radiation therapy ) |
| Radiation TherapyAlso: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, IrradiatedUndergo radiation therapy | Radiation | Group 1 (pembrolizumab, surgery, temozolomide, radiation), Group 2 (pembrolizumab, temozolomide, radiation therapy ) |
| TemozolomideAlso: 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 39831Given PO | Drug | Group 1 (pembrolizumab, surgery, temozolomide, radiation), Group 2 (pembrolizumab, temozolomide, radiation therapy ) |
| Therapeutic Conventional SurgeryUndergo surgery | Procedure or surgery | Group 1 (pembrolizumab, surgery, temozolomide, radiation) |
Primary outcome
Incidence of Dose Limiting Toxicities
Time frame: 189 days
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.
Group 2 Overall Survival (OS) at 18 Months
Time frame: 18 months
Defined as the number of patients who are alive up to 18 months after beginning study therapy.
5 secondary outcomes
Incidence of Adverse Events
Time frame: 14 months
Time Until Treatment Related Grade 3+ Adverse Event
Time frame: 14 months
Time to Progression (Group 2)
Time frame: 36 months
Progression-free Survival (Group 2)
Time frame: 36 months
Time to Treatment Failure (Group 2)
Time frame: 13 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ian F. Parney, MD, PhD principal investigator
Mayo Clinic in Rochester
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing External Beam Radiation Therapy, Laboratory Biomarker Analysis and Pembrolizumab in people with Glioblastoma and Gliosarcoma, run by Mayo Clinic at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose Limiting Toxicities (time frame: 189 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.