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Clinical Trial 19342

Cancer Type: Neurologic Oncology
Study Type: Treatment
NCT#: NCT03426891

Phase: Phase I
Principal Investigator:

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Study Title

A Phase I Trial of Pembrolizumab and Vorinostat Combined with Temozolomide and Radiation Therapy for Newly Diagnosed Glioblastoma


The purpose of this research study is to test the safety and tolerability of the combination treatment of the investigational drugs vorinostat and pembrolizumab, in combination with chemotherapy (temozolomide), and radiotherapy.


Primary: To evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) of pembrolizumab given in combination with vorinostat, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma. Secondary:: To evaluate the 12 months and 24 months survival rate in patients with newly diagnosed glioblastoma who are treated with pembrolizumab in combination with vorinostat and standard treatment with radiotherapy and temozolomide. Exploratory: To explore tissue and blood biomarkers that may predict tumor response to pembrolizumab in combination with vorinostat and standard treatment with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma.



Chemotherapy (NOS); Immunotherapy; Radiotherapy


Pembrolizumab (Keytruda); SAHA (Vorinostat); Temodal (Temozolomide); Temozolomide (); Vorinostat (); Zolinza (Vorinostat); suberoylanilide hydroxamic acid (Vorinostat)

Inclusion Criteria

  • Newly diagnosed glioblastoma or gliosarcoma
  • Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma
  • An interval of > 21 days since surgical resection prior to treatment on the trial
  • Karnofsky performance status of 70 or higher
  • Adequate organ function laboratory values
  • Resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest
  • Willing and able to provide written informed consent/assent for the trial.
  • Life expectancy >12 weeks
  • Willingness to discontinue medications known to be associated with risk of Torsades de Pointes such as quinidine, procainamide, disopyramide, amiodarone, erythromycin, clarithromycin, chlorpromazine and haloperidol
  • Single lesion less than 4 cm in longest diameter (diameter of enhancing lesion)
  • Patient shouldn't have received any anti-cancer therapy for glioblastoma in past
  • Females of childbearing potential (FOCBP) should have a negative urine or serum pregnancy prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Females and males of childbearing potential must agree to use an adequate method of contraception as outlined in study documentation,starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception.
  • Use of Optune device is allowed.

  • Exclusion Criteria

  • Has had prior treatment of glioblastoma (GBM) with radiation and temozolomide
  • Evidence of leptomeningeal disease
  • Prior treatment with Gliadel
  • Unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Physiologic doses of steroid therapy (≤ 2 mg/day dexamethasone equivalents) by the time of first dose of treatment are allowed.
  • Known history of active Bacillus Tuberculosis (TB)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Potential participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • A known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded.
  • Known history or any evidence of active, interstitial lung disease or non-infectious pneumonitis requiring corticosteroid therapy
  • Active serious infection requiring systemic therapy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to day 1 of treatment on study
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the patient to participate
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

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