Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma

  • STATUS
    Recruiting
  • End date
    Jul 31, 2022
  • participants needed
    50
  • sponsor
    Mayo Clinic
Updated on 26 January 2021
platelet count
cancer
serum pregnancy test
direct bilirubin
MRI
erythropoietin
neutrophil count
tumor cells
blood transfusion
external beam radiation therapy
aptt
thromboplastin
glioblastoma multiforme
temozolomide
astrocytoma
gliosarcoma
supratentorial glioblastoma multiforme
beam radiation
stereotactic biopsy

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.

Description

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.

Details
Condition Glioma, gliosarcoma, Glioblastoma Multiforme, Supratentorial Glioblastoma, Gliomas, glioblastoma, supratentorial glioblastoma multiforme
Treatment radiation therapy, laboratory biomarker analysis, Temozolomide, Pembrolizumab, therapeutic conventional surgery, external beam radiation therapy
Clinical Study IdentifierNCT03197506
SponsorMayo Clinic
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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 from a prior stereotactic biopsy
NOTE: Stereotactic biopsy must have been =< 28 days prior to registration
Neoadjuvant patients only: Willing to undergo craniotomy and resection of their glioblastoma at Mayo Clinic in Rochester, Minnesota (MN)
Adjuvant patients only: Must have undergone craniotomy and resection of their glioblastoma =< 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
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