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Trial record 3 of 5 for:    svn53

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02455557
Recruitment Status : Active, not recruiting
First Posted : May 28, 2015
Last Update Posted : December 7, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE May 22, 2015
First Posted Date  ICMJE May 28, 2015
Last Update Posted Date December 7, 2020
Actual Study Start Date  ICMJE May 4, 2015
Actual Primary Completion Date October 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
Progression-free survival (PFS) [ Time Frame: Date of diagnosis to the date of first observed disease progression or death due to any cause, assessed at 6 months ]
Estimated as standard binomial proportion. An exact one-sided binomial test will be used to test primary hypothesis. The nominal significance level to be used for this test is 0.10. In addition, a Kaplan-Meier curve for PFS will be used calculated to generate summary descriptive statistics, e.g. median PFS.
Original Primary Outcome Measures  ICMJE
 (submitted: May 22, 2015)
Progression-free survival (PFS) [ Time Frame: Date of diagnosis to the date of first observed disease progression or death due to any cause, assessed up to 2 years ]
The PFS distribution will be estimated using the Kaplan-Meier method. Using this distributional estimate, summary descriptive statistics, e.g. percentiles, will be obtained. A one-sided 95% confidence interval for the median using the methodology of Brookmeyer and Crowley will be calculated and compared to the historical median in order to statistically assess improvement by the study treatment. The nominal significance level to be used for this test is 0.05.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2015)
  • Immune responses to SurVaxM and predictors of response [ Time Frame: Up to 30 days after completion of study treatment ]
    A series of exploratory analyses will initially take place including individual subject-level profile plots and overall mean plots used to examining the mean structure. Formal statistical examination of longitudinal patterns will be done through the use of a mixed model. Restricted maximum likelihood estimation will be utilized in the model fitting procedures. Once the model is fit, specific linear contrasts based on the estimated model parameters will be constructed and used to test hypotheses concerning between time point comparisons.
  • Incidence of grade 3 or 4 toxicities, according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 4 [ Time Frame: Up to 30 days after completion of study treatment ]
    Toxicity rate will be estimated using simple relative frequencies. The corresponding 95% confidence intervals for the estimated probabilities will be computed using the method proposed in Clopper and Pearson.
  • Overall survival [ Time Frame: Date of diagnosis until (1) date of death or (2) the last date patient known alive (if death is not observed), assessed up to 2 years ]
    The estimated distributions of overall survival will be obtained using the Kaplan-Meier method. Estimates of quantities such as median survival will be obtained. Corresponding confidence intervals will be computed.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SurVaxM Vaccine Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
Official Title  ICMJE A Phase II Study of the Safety and Efficacy of SVN53-67/M57-KLH (SurVaxM) in Survivin-Positive Newly Diagnosed Glioblastoma
Brief Summary 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 6-month progression-free survival (PFS6) in patients with survivin positive newly diagnosed glioblastoma multiforme (GBM) treated with at least 4 doses of SVN53-67/M57-keyhole limpet hemocyanin (KLH) peptide vaccine (SurVaxM) and standard of care 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 7-28 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Gliosarcoma
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Montanide ISA 51 VG
    Given SC
  • Biological: Sargramostim
    Given SC
    Other Names:
    • 23-L-Leucinecolony-Stimulating Factor 2
    • DRG-0012
    • Leukine
    • Prokine
    • rhu GM-CFS
    • Sagramostim
    • Sargramostatin
  • Biological: SVN53-67/M57-KLH Peptide Vaccine
    Given SC
  • Drug: Temozolomide
    Given PO or IV
    Other Names:
    • 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
    • Temcad
    • Temodal
    • Temodar
    • Temomedac
Study Arms  ICMJE Experimental: Treatment (SurVaxM, temozolomide)
Patients receive the first priming dose of SVN53-67/M57-KLH peptide vaccine in emulsion with montanide ISA 51 SC and sargramostim SC within 7-28 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.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Drug: Montanide ISA 51 VG
  • Biological: Sargramostim
  • Biological: SVN53-67/M57-KLH Peptide Vaccine
  • Drug: Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 26, 2018)
64
Original Estimated Enrollment  ICMJE
 (submitted: May 22, 2015)
50
Estimated Study Completion Date  ICMJE January 30, 2021
Actual Primary Completion Date October 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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); or World Health Organization (WHO) grade IV [gliosarcoma]
  • 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
  • Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet 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)
  • Creatinine =< 1.8 mg/dl
  • Human leukocyte antigen (HLA)-A*02, HLA-A*03, HLA-A*11 or 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; Patients with increased or new gadolinium enhancement may continue on protocol if in the investigator's judgment that enhancement is likely due to pseuodoprogresion. The use of correlative imaging studies (including PWI) or diffusion weighted imaging (DWI) and repeat imaging after an interval of 2-4 weeks is strongly encouraged to help distinguish between pseudoprogression and true progression.
  • Magnetic resonance imaging (MRI) (ideally completed within 96 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 1 cm 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 physician's 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02455557
Other Study ID Numbers  ICMJE I 259614
NCI-2015-00694 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 259614 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Robert Fenstermaker Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP