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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

Primary Purpose

Malignant Pleural Mesothelioma (MPM)

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Multipeptide vaccine S-588210
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma (MPM) focused on measuring mesothelioma, multipeptide vaccine, S-588210

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Weekly Vaccination

Every other Week Vaccination

Arm Description

Maintenance multipeptide vaccine (S-588210) administered every week

Maintenance multipeptide vaccine (S-588210) administered every other week

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03
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)
6-month progression-free survival (PFS) rate
Peptide-specific cytotoxic T lymphocyte response determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay

Full Information

First Posted
January 20, 2016
Last Updated
May 7, 2018
Sponsor
University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT02661659
Brief 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
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Withdrawn
Why Stopped
PI stopped study due to inability to accrue.
Study Start Date
June 12, 2016 (Actual)
Primary Completion Date
October 3, 2017 (Actual)
Study Completion Date
October 3, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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: To evaluate the safety of S-588210 in HLA-A*02:01-positive patients with MPM treated with S-588210 To determine the disease control rate (DCR) in HLA-A*02:01-positive patients with MPM treated with S-588210 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 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma (MPM)
Keywords
mesothelioma, multipeptide vaccine, S-588210

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Weekly Vaccination
Arm Type
Other
Arm Description
Maintenance multipeptide vaccine (S-588210) administered every week
Arm Title
Every other Week Vaccination
Arm Type
Other
Arm Description
Maintenance multipeptide vaccine (S-588210) administered every other week
Intervention Type
Biological
Intervention Name(s)
Multipeptide vaccine S-588210
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Time Frame
Up to 4 weeks
Title
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
Title
6-month progression-free survival (PFS) rate
Time Frame
6 months
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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: 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) radiotherapy for the target disease 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
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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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