Clinical Trials /

Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma

NCT03197506

Description:

This phase II trial studies the side effects and how well pembrolizumab works in combination with standard therapy in treating patients with glioblastoma. Drugs used in the chemotherapy, such as pembrolizumab and 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.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma
  • Official Title: Phase II Study of Pembrolizumab (MK-3475) in Combination With Standard Therapy for Newly Diagnosed Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: MC1572
  • SECONDARY ID: NCI-2017-01106
  • SECONDARY ID: MC1572
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03197506

Conditions

  • Glioblastoma
  • Gliosarcoma
  • Supratentorial Glioblastoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, standard therapy)
TemozolomideCCRG-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, TemomedacTreatment (pembrolizumab, standard therapy)

Purpose

This phase II trial studies the side effects and how well pembrolizumab works in combination with standard therapy in treating patients with glioblastoma. Drugs used in the chemotherapy, such as pembrolizumab and 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:

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

      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.

      III. To assess progression-free survival in patients treated with pembrolizumab in
      combination with standard therapy in patients with newly diagnosed GBM.

      IV. To assess time to treatment failure in patients treated with pembrolizumab in combination
      with standard therapy in patients with newly diagnosed GBM.

      TERTIARY 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.

      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:

      NEOADJUVANT (COURSE 1): Patients receive pembrolizumab intravenously (IV) over 30 minutes on
      day 1.

      SURGERY (COURSE 2): Patients undergo standard of care surgery within days 4-7.

      CONCURRENT (COURSE 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 (COURSE 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 courses in the absence of disease
      progression or unexpected toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 3-4
      months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, standard therapy)ExperimentalNEOADJUVANT (COURSE 1): Patients receive pembrolizumab IV over 30 minutes on day 1. SURGERY (COURSE 2): Patients undergo standard of care surgery within days 4-7. CONCURRENT (COURSE 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 (COURSE 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 courses in the absence of disease progression or unexpected toxicity.
  • Pembrolizumab
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          -  Histological confirmation of supratentorial glioblastoma (also known as astrocytoma
             grade IV, gliosarcoma) amenable to surgical resection =< 28 days prior to registration

          -  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

          -  Willing to undergo craniotomy and resection of their glioblastoma

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dL without transfusion or erythropoietin (EPO) dependency (=< 7
             days prior to assessment)

          -  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

          -  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

          -  Albumin >= 2.5 mg/dL

          -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total
             bilirubin levels > 1.5 x ULN

          -  Aspartate transaminase (AST) AND alanine transaminase (ALT) =< 2.5 x ULN

          -  Creatinine =< 1.0 x ULN OR measured or calculated creatinine clearance (per
             institutional standard) must be >= 60 ml/min

          -  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 women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  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); 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities
Time Frame:Up to 5 years
Safety Issue:
Description:Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number and severity of all adverse events will be tabulated and summarized in this patient population.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

December 10, 2019