PERGOLA: PEMBROLIZUMAB FOR NEWLY DIAGNOSED GLIOBLASTOMA: A PROSPECTIVE, OPEN-LABEL, SINGLE-ARM, MULTICENTER PHASE II STUDY
Indication :

Glioblastome nouvellement diagnostiqué


Sponsor :

University Hospital Zurich


Phase :

II


Ligne :

première


Traitement :

radiothérapie + temozolomide + pembrolizumab


Site :

CHUV


Contact(s) :
Andreas Hottinger
Investigateur Principale

CHUV
Département d'oncologie

Rue du Bugnon 46
Lausanne
1011

021 314 65 41
andreas.hottinger@chuv.ch

Primary objective :

To explore whether the addition of pembrolizumab to standard temozolomide-based radiochemotherapy improves the outcome of newly diagnosed glioblastoma or gliosarcoma patients, determined by the overall survival rate at 12 months.


Inclusion criteria :
  • Newly diagnosed glioblastoma or gliosarcoma as confirmed by local histopathology
  • The patient is at least 18 years of age on day of signing informed consent
  • Absence of IDH1 R132H mutation by immunohistochemistry
  • A maximum dose of 4 mg/day dexamethasone or equivalent doses for other corticosteroids, which has been stable or decreased for ≥5 days prior to start of radiotherapy
  • Patient who are treated with anticoagulants are on a stable dose for at least two weeks prior to start of radiotherapy
  • The patient is male or a non-pregnant, non-lactating female
  • The patient has a life expectancy of at least 3 months
  • The patient has an ECOG performance score of 0 or 1
  • The patient shows adequate organ functions as assessed by the following laboratory values within 2 weeks prior to first dose of study medication:
  • Adequate renal function determined by serum creatinine and urea < 2 times the upper limit of normal
  • Adequate liver function with ALT, AST and AP < 3 times the upper limit of normal, and bilirubin value < 2.5 mg/dL
  • INR and aPTT within therapeutic limits (according to the medical standard at the institution)
  • Hemoglobin > 9 g/dL
  • Platelet count > 100 x 109/L
  • WBC > 3 x 109/L
  • ANC > 1.5 x 109/L
  • Patient is able to undergo Gd MRI.

Exclusion criteria :
  • Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to temozolomide or pembrolizumab
  • Is currently participating and receiving study therapy or has participated in a study within 4 weeks of the first dose of treatment
  • Any known IDH mutation if tested
  • Has a diagnosis of immunodeficiency
  • HIV, HBV or HCV infection
  • Has a history of active TB (Bacillus Tuberculosis)
  • Clinically relevant acute viral, bacterial, or fungal infection
  • History of a second independent malignant disorder during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with PSA level less than upper normal limit
  • Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Prior radiotherapy to the brain or interstitial brachytherapy
  • Prior chemotherapy for a brain tumor
  • Intraoperative placement of carmustine wafers (Gliadel®)
  • Prior therapy with immune checkpoint inhibitors or vaccination therapy against the tumor
  • Concurrent administration of any antitumor therapy other than TMZ/RT=>TMZ
  • Clinically relevant psychiatric disorders/legal incapacity or a limited legal capacity
  • Has received a live vaccine within 30 days of planned start of study therapy