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A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy

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ClinicalTrials.gov Identifier: NCT02661659
Recruitment Status : Withdrawn (PI stopped study due to inability to accrue.)
First Posted : January 22, 2016
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Study Description
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Brief Summary:
A phase Ib study investigating the safety, the immunogenicity and the optimal administration frequency of the S-588210 5-peptide vaccine in MPM patients without progression after pemetrexed-based chemotherapy will be conducted. Additionally, to identify more accurate predictive biomarkers of response to S-588210, T-cell-receptor-sequencing (TCR) pre- and post-vaccination will be performed in blood samples of patients treated with the vaccine. Immunohistochemical analysis of the vaccine oncoantigens will also be correlated with induction of antigen-specific T-cell responses. Finally, to explore the infiltration of tumors with T-cells and the potential presence of an immunosuppressive tumor microenvironment, immunohistochemistry for immune checkpoints (including PDL1/PD1, CTLA4) and immune suppressive cell subsets (T-regs, macrophages) will be performed.

Condition or disease Intervention/treatment Phase
Malignant Pleural Mesothelioma (MPM) Biological: Multipeptide vaccine S-588210 Phase 1

Detailed Description:

Primary Objective:

To evaluate the rate of peptide-specific CTL induction to S-588210 within the first 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy treated on a weekly or every other week vaccination schedule.

Secondary Objectives:

  1. To evaluate the safety of S-588210 in HLA-A*02:01-positive patients with MPM treated with S-588210
  2. To determine the disease control rate (DCR) in HLA-A*02:01-positive patients with MPM treated with S-588210
  3. To determine the progression-free-survival (PFS) in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy and who are treated with S-588210
  4. To evaluate the peptide-specific CTL response to S-588210 over time up to 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy
Actual Study Start Date : June 12, 2016
Actual Primary Completion Date : October 3, 2017
Actual Study Completion Date : October 3, 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Weekly Vaccination
Maintenance multipeptide vaccine (S-588210) administered every week
 Biological: Multipeptide vaccine S-588210
Every other Week Vaccination
Maintenance multipeptide vaccine (S-588210) administered every other week
 Biological: Multipeptide vaccine S-588210


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of patients who show in vitro cytotoxic T lymphocyte induction to at least 2 of the 5 antigens determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay [ Time Frame: Within 8 months from initiation of vaccination ]

Secondary Outcome Measures :
  1. Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [ Time Frame: Up to 4 weeks ]
  2. Disease control rate defined as the proportion of patients who are assessed as having complete response (CR), partial response (PR), or stable disease (SD) (>3 months) [ Time Frame: 6 months ]
  3. 6-month progression-free survival (PFS) rate [ Time Frame: 6 months ]
  4. Peptide-specific cytotoxic T lymphocyte response determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay [ Time Frame: At 2, 3, 4, 6 and 8 months of vaccination ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with unresectable MPM that have completed 4-6 cycles of standard first-line pemetrexed-based chemotherapy for at least 1 month and have not progressed
  • Age>18
  • Able to provide informed consent for the study
  • HLA-A*02:01 positive
  • ECOG PS=0-1 at enrollment
  • Measurable indicator lesion by modified RECIST criteria
  • Adequate bone marrow (ANC > 1000cells/ml, PLT > 50,000/ml, Hg > 8gr/dL), renal (Cr > 2.5xUNL) and liver function (AST, ALT< 3x UNL, total bilirubin < 2x UNL, ALP < 3x UNL)
  • Archival tumor tissue available for IHC (1 paraffin-embedded block)
  • Epithelioid or biphasic histology

Exclusion Criteria:

  • Chemotherapy or investigational antineoplastic drug within 1 month of planned initiation of vaccine therapy
  • Patients who received DEPDC1, MPHOSPH1, URLC10, CDCA1, or KOC1 peptide vaccines before
  • Active treatment with corticosteroids or other immunosuppressive agents

  • Patients who are expected to require any of the following therapies between enrollment and completion or discontinuation of the study treatment:

    1. immunosuppressive drugs, including corticosteroids, methotrexate, mercaptopurine, azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, ATG (anti-thymoglobulin), IL2-receptor antibodies (basiliximab, daclizumab), TNF-a antibodies (infliximab, etanercept, adalimumab)
    2. radiotherapy for the target disease
    3. surgical therapy for the target disease
  • History of bone marrow transplantation
  • Active infection
  • Human immunodeficiency virus infection
  • History of or active systemic autoimmune disorder or immunodeficiency syndromes
  • History of severe (CTCAE v.4.03 grade 3 or higher) allergic reaction to a drug, vaccination, or biological preparation.
  • Pregnancy
  • Patients who cannot or do not intend to practice effective contraception
  • Severe illness requiring hospitalization
  • Lymphocytes <15% of total WBCs at baseline
  • Sarcomatoid histology
  • Severe (CTCAE v.4.03 grade 3 or higher) concurrent hepatic impairment, renal impairment, heart disease, hematological disease, respiratory disease, or metabolic disease
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02661659


Locations
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United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
More Information
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02661659    
Other Study ID Numbers: IRB14-1519
First Posted: January 22, 2016    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Keywords provided by University of Chicago:
mesothelioma
multipeptide vaccine
S-588210
Additional relevant MeSH terms:
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Mesothelioma
Mesothelioma, Malignant
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
 Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases