Clinical Trials /

Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence

NCT04013672

Description:

The main purpose of this study is to assess the clinical activity of Pembrolizumab and SurVaxM in participants with recurrent glioblastoma.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence
  • Official Title: Phase II Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence

Clinical Trial IDs

  • ORG STUDY ID: CASE6318
  • NCT ID: NCT04013672

Conditions

  • Recurrent Glioblastoma

Interventions

DrugSynonymsArms
PembrolizumabArm A - Have not received immunotherapy
SurVaxMSVN53-67, M57-KLHArm A - Have not received immunotherapy
SargramostimGM-CSFArm A - Have not received immunotherapy
Montanide ISA 51Arm A - Have not received immunotherapy

Purpose

The main purpose of this study is to assess the clinical activity of Pembrolizumab and SurVaxM in participants with recurrent glioblastoma.

Detailed Description

      Primary objective: Assess clinical activity of Pembrolizumab and SurVaxM in participants with
      recurrent glioblastoma using progression free survival at 6 months (PFS-6).

      Secondary objective: : Assess safety and tolerability of Pembrolizumab and SurVaxM in
      participants with recurrent glioblastoma.

      This is a Phase II study of two arms in participants with recurrent glioblastoma. Arm A will
      include participants with first recurrence of glioblastoma who have failed prior chemotherapy
      and radiation but have not received any immunotherapy. Arm B is an exploratory arm of 10
      participants who have failed prior anti-PD1 therapy.

      All patients will receive the study drug combination consisting of SurVaxM and pembrolizumab
      (PEM) with no randomization, stratification or dose escalation.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A - Have not received immunotherapyExperimentalArm A is patients with first recurrence of glioblastoma who have failed prior chemotherapy and radiation but have not received any immunotherapy.
  • Pembrolizumab
  • SurVaxM
  • Sargramostim
  • Montanide ISA 51
Arm B - Have failed prior anti-PD1 therapyExperimentalArm B is an exploratory arm of 10 patients who have failed prior anti-PD1 therapy.
  • Pembrolizumab
  • SurVaxM
  • Sargramostim
  • Montanide ISA 51

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of World Health Organization Grade IV glioma
             (glioblastoma or gliosarcoma)

          -  Previous first line treatment with at least radiotherapy with or without temozolomide

          -  Documented first recurrence of GBM by diagnostic biopsy or contrast enhanced magnetic
             resonance imaging (MRI) performed within 21 days of randomization per RANO criteria.

          -  If first recurrence of GBM is documented by MRI, an interval of at least 12 weeks
             after the end of prior radiation therapy is required unless there is either:

             -- Histopathologic confirmation of recurrent tumor, or

             -- New enhancement on MRI outside of the radiotherapy treatment field

          -  Karnofsky performance status of 70 or higher or ECOG 0-2

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the
             start of study drug.

          -  Previous treatment with anti PD1 will be allowed only in the exploratory arm

          -  The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial.

          -  Have provided archival tumor tissue sample or newly obtained core or excisional biopsy
             of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
             tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
             archive tissue

          -  Screening/Baseline laboratory values must meet the following criteria (laboratory
             value):

             --Note: This table includes eligibility-defining laboratory value requirements for
             treatment; laboratory value requirements should be adapted according to local
             regulations and guidelines for the administration of specific chemotherapies.

             ---Hematological system:

               -  Absolute neutrophil count (ANC) ≥1500/uL

               -  Platelets ≥100 000/µL

               -  Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin
                  dependency and without packed red blood cell (pRBC) transfusion within last 2
                  weeks.)

                  ---Renal system:

               -  Creatinine OR Measured or calculated (Creatinine clearance (CrCl) should be
                  calculated per institutional standard) creatinine clearance (GFR can also be used
                  in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with
                  creatinine levels >1.5 × institutional ULN

                  ---Hepatic system:

               -  Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
                  bilirubin levels >1.5 × ULN

               -  AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver
                  metastases)

                  --- Coagulation system:

               -  International normalized ratio (INR) OR prothrombin time (PT) Activated partial
                  thromboplastin time (aPTT): ≤1.5 × ULN unless participant is receiving
                  anticoagulant therapy as long as PT or aPTT is within therapeutic range of
                  intended use of anticoagulants

          -  Male participants:

             --A male participant must agree to use a contraception as detailed in Appendix 3 of
             this protocol during the treatment period and for at least 180 days after the last
             dose of study treatment and refrain from donating sperm during this period.

          -  Female participants:

               -  A female participant is eligible to participate if she is not pregnant (see
                  Appendix 3), not breastfeeding, and at least one of the following conditions
                  applies:

                    -  Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR

                    -  A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during
                       the treatment period and for at least 180 days after the last dose of study
                       treatment.

        Exclusion Criteria:

          -  A WOCBP who has a positive urine pregnancy test within 72 hours prior to If the urine
             test is positive or cannot be confirmed as negative, a serum pregnancy test will be
             required.

          -  Has received prior therapy with an anti-PD-1 (except in the exploratory arm),
             anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or
             co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).

          -  Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks [could consider shorter interval for kinase inhibitors or other short
             half-life drugs] prior to (randomization /allocation).

               -  Note: Participants must have recovered from all AEs due to previous therapies to
                  ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.

               -  Note: If participant received major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  study treatment.

          -  Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment.

             --Note: Participants who have entered the follow-up phase of an investigational study
             may participate as long as it has been 4 weeks after the last dose of the previous
             investigational agent.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 2 mg daily of dexamethasone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          -  Patients that likely to have the potential risk of cerebral edema due to inflammation
             related to SurVaxM and pembrolizumab and will exclude patients with > 1 cm midline
             shift on imaging. Patients ust not have cerebral edema requiring more than 2 mg of
             daily of dexamethasone equivalent.

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
             cervical cancer in situ) that have undergone potentially curative therapy are not
             excluded.

          -  More than one recurrence of GBM

          -  Presence of extracranial metastatic or leptomeningeal disease

          -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

          -  Has 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 (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active infection requiring systemic therapy .Has a known history of Human
             Immunodeficiency Virus (HIV). No HIV testing is required

          -  Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
             detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
             unless mandated by local health authority.

          -  Has a known history of active TB (Bacillus Tuberculosis).

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of trial treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:6 months from start of treatment
Safety Issue:
Description:Assess clinical activity of Pembrolizumab and SurVaxM in patients with recurrent glioblastoma using PFS at 6 months (PFS-6)

Secondary Outcome Measures

Measure:Safety and tolerability of Pembrolizumab and SurVaxM as measure by CTCAE v 5 grading as per NCI
Time Frame:up to 1 year from enrollment
Safety Issue:
Description:Safety and tolerability of Pembrolizumab and SurVaxM in patients with recurrent glioblastoma measured on ongoing basis with CTCAE v 5 grading as per NCI. Grade 1-2 and 3-5 events will be recorded and reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Manmeet Ahluwalia, MD

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