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SurVaxM Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

NCT02455557

Description:

This phase II trial studies the side effects and how well vaccine therapy works when given together with temozolomide in treating patients with newly diagnosed glioblastoma. Vaccines made from the survivin peptide or antigen may help the body build an effective immune response to kill tumor cells that express survivin. Drugs used in 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. It is not yet known whether temozolomide is more effective with or without vaccine therapy in treating glioblastoma.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

SurVaxM Vaccine Therapy and <span class="go-doc-concept go-doc-intervention">Temozolomide</span> in Treating Patients With Newly Diagnosed <span class="go-doc-concept go-doc-disease">Glioblastoma</span>

Title

  • Brief Title: SurVaxM Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
  • Official Title: A Phase II Study of the Safety and Efficacy of SVN53-67/M57-KLH (SurVaxM) in Survivin-Positive Newly Diagnosed Glioblastoma
  • Clinical Trial IDs

    NCT ID: NCT02455557

    ORG ID: I 259614

    NCI ID: NCI-2015-00694

    Trial Conditions

    Glioblastoma

    Trial Interventions

    Drug Synonyms Arms
    Montanide ISA 51 VG Treatment (SurVaxM, temozolomide)
    Temozolomide CCRG-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, Temodal, Temodar Treatment (SurVaxM, temozolomide)

    Trial Purpose

    This phase II trial studies the side effects and how well vaccine therapy works when given
    together with temozolomide in treating patients with newly diagnosed glioblastoma. Vaccines
    made from the survivin peptide or antigen may help the body build an effective immune
    response to kill tumor cells that express survivin. Drugs used in 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. It is not yet
    known whether temozolomide is more effective with or without vaccine therapy in treating
    glioblastoma.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To evaluate progression-free survival (PFS) in patients with survivin positive newly
    diagnosed glioblastoma multiforme (GBM) treated with SurVaxM (SVN53-67/M57-keyhole limpet
    hemocyanin [KLH] peptide vaccine) and adjuvant temozolomide.

    SECONDARY OBJECTIVES:

    I. To determine the safety and tolerability of SurVaxM in patients receiving standard care
    adjuvant temozolomide.

    II. To evaluate overall survival (OS) in patients with survivin positive newly diagnosed GBM
    treated with SurVaxM and adjuvant temozolomide.

    III. To describe the immune response in patients treated with SurVaxM and predictors of
    response.

    IV. To evaluate objective tumor response rate (applicable only for patients with evaluable
    disease at study entry, as defined per Response Assessment in Neuro-Oncology [RANO]
    criteria) and predictors of response.

    OUTLINE:

    Patients receive the first priming dose of SVN53-67/M57-KLH peptide vaccine in emulsion with
    montanide ISA 51 subcutaneously (SC) and sargramostim SC within 7-14 days after completion
    of chemoradiation. Treatment repeats every 2 weeks for a total of 4 doses in the vaccine
    priming phase and then every 12 weeks during the adjuvant phase in the absence of disease
    progression or unacceptable toxicity. Patients also receive standard adjuvant temozolomide
    orally (PO) or intravenously (IV) on days 1-5. Treatment repeats every 28 days for 6 courses
    or more (at the discretion of the investigator) in the absence of disease progression or
    unacceptable toxicity. Patients may then receive maintenance SVN53-67/M57-KLH peptide
    vaccine in emulsion with montanide ISA 51 SC and sargramostim SC every 12 weeks in the
    absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up every 12 weeks.

    Trial Arms

    Name Type Description Interventions
    Treatment (SurVaxM, temozolomide) Experimental Patients receive the first priming dose of SVN53-67/M57-KLH peptide vaccine in emulsion with montanide ISA 51 SC and sargramostim SC within 7-14 days after completion of chemoradiation. Treatment repeats every 2 weeks for a total of 4 doses in the vaccine priming phase and then every 12 weeks during the adjuvant phase in the absence of disease progression or unacceptable toxicity. Patients also receive standard adjuvant temozolomide PO or IV on days 1-5. Treatment repeats every 28 days for 6 courses or more (at the discretion of the investigator) in the absence of disease progression or unacceptable toxicity. Patients may then receive maintenance SVN53-67/M57-KLH peptide vaccine in emulsion with montanide ISA 51 SC and sargramostim SC every 12 weeks in the absence of disease progression or unacceptable toxicity. Montanide ISA 51 VG, Temozolomide

    Eligibility Criteria

    Inclusion Criteria:

    - Have a Karnofsky performance status >= 70 (i.e. the patient must be able to care for
    himself/herself with occasional help from others)

    - Documented survivin-positive tumor status

    - Pathologically confirmed diagnosis of glioblastoma multiforme (GBM)

    - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

    - Platelets >= 100 x 10^9/L

    - Hemoglobin (Hgb) > 9.0 g/dL

    - Serum total bilirubin: =< 1.5 x upper limit of normal (ULN)

    - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 4.0 x ULN

    - Blood coagulation parameters: international normalized ratio (INR) =< 1.5 for
    patients not on warfarin

    - Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW]
    heparin must meet both of the following criteria:

    - No active bleeding or pathological condition that carries a high risk of
    bleeding (e.g., tumor involving major vessels or known varices)

    - In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a
    stable dose of low molecular weight heparin

    - Creatinine =< 1.8 mg/dl

    - Human leukocyte antigen (HLA)-A*02, HLA-A*03, HLA-A*11 and HLA-A*24 positive patients

    - No evidence of progressive disease from the postoperative period to the
    post-chemoradiation period, based on changes in the neurologic exam steroid use, or
    evident radiographic progression, according to RANO criteria

    - Magnetic resonance imaging (MRI) (ideally completed within 72 hours after surgery)
    documenting gross total resection consisting of no gadolinium enhancement; or
    subtotal resection consisting of linear enhancement with (or without) nodular
    gadolinium enhancement measuring no greater than 1 cm x 1 cm x 1cm total volume or
    100 mm^2 in cross sectional area

    - Participants of child-bearing potential must agree to use adequate contraceptive
    methods (e.g., hormonal or barrier method of birth control; abstinence) prior to
    study entry, and have a negative pregnancy test prior to starting study treatment;
    should a woman become pregnant or suspect she is pregnant while she or her partner is
    participating in this study, she should inform her treating physician immediately

    - Dexamethasone dose less than or equal to 4 mg daily at time of study enrollment

    - Patients must have completed initial radiation therapy (RT) and temozolomide (TMZ)
    for the treatment of their glioblastoma (i.e., completed 6-week course of RT and,
    completed >= 75% of 6-week course of induction TMZ chemotherapy)

    - Participant or legal representative must understand the investigational nature of
    this study and sign an Independent Ethics Committee/Institutional Review Board
    approved written informed consent form prior to receiving any study related procedure

    Exclusion Criteria:

    - The patient must not have received any immunotherapy for their brain tumor

    - Patients with serious concurrent infection or medical illness, which in the treating
    physicians opinion would jeopardize the ability of the patient to receive the
    treatment outlined in this protocol with reasonable safety

    - Patients who are pregnant or breast-feeding

    - Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or
    investigational agents) other than temozolomide

    - Patients with a concurrent or prior malignancy are ineligible unless they are
    patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the
    skin; patients who have been free of disease (any prior malignancy) for at least 3
    years are eligible for this study

    - Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ
    treatment

    - Patients who received other chemotherapeutics or investigational agents in addition
    to their radiation therapy and concomitant temozolomide treatment

    - Patients who have received Gliadel wafers or alternating electrical field therapy
    (ETTF) are not eligible for this study

    - Known history of an autoimmune disorder

    - Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency
    syndrome (AIDS) related illness or other serious medical illness

    - Patients who have contraindication to MRI

    - Unwilling or unable to follow protocol requirements

    - Any condition which in the investigator's opinion deems the participant an unsuitable
    candidate to receive study drug

    - Received an investigational agent within 30 days prior to registration

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival (PFS)

    Secondary Outcome Measures

    Immune responses to SurVaxM and predictors of response

    Incidence of grade 3 or 4 toxicities, according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 4

    Overall survival

    Trial Keywords