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Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT04117087
Recruitment Status : Not yet recruiting
First Posted : October 7, 2019
Last Update Posted : October 7, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE October 3, 2019
First Posted Date  ICMJE October 7, 2019
Last Update Posted Date October 7, 2019
Estimated Study Start Date  ICMJE January 2020
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
  • Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]
    Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
  • Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 16 weeks [ Time Frame: Baseline, 16 weeks ]
    Evaluated by the fold change in interferon-producing mutant-KRAS-specific cluster of differentiation 8 (CD8) and cluster of differentiation 4 (CD4) T cells after vaccination at 16 weeks compare to pre-vaccination baseline.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
  • Number of months from the date of first treatment until first documented disease recurrence or death [ Time Frame: 4 years ]
    Number of months from the date of first treatment until first documented disease recurrence or death. This will be used to assess Disease-free Survival (DFS).
  • Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells [ Time Frame: Baseline, 4 years ]
    Percent change pre-vaccination baseline compared to end of study.
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 Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer
Official Title  ICMJE Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer
Brief Summary Phase 1 study for patients with resected PDAC and mismatch repair (MMR)-p colorectal cancer (CRC) to evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with poly-ICLC adjuvant in combination with nivolumab and ipilimumab after adjuvant standard of care treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Pancreatic Cancer
Intervention  ICMJE
  • Drug: KRAS peptide vaccine
    1. KRAS peptide vaccine will be administered on days 1, 8, 15 and 22. Five boost vaccinations with will be administered at 8-9 week intervals (on weeks 13, 22, 31, 40, and 49).
    2. Drug: 1.8 mg KRAS peptide vaccine + 0.3mg Poly-ICLC
    Other Name: Hiltonol® (Poly-ICLC)
  • Drug: Nivolumab
    1. Nivolumab 360 mg will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of each 21 day cycle.
    2. Drug: 360 mg IV
    Other Name: OPDIVO
  • Drug: Ipilimumab
    1. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of Cycles 1, 3, 5, 7, 9, 11, 13, 15 and 17 of the study or every 6 weeks for a total of a year.
    2. Drug: 1mg/kg IV
    Other Name: YERVOY®
Study Arms  ICMJE Experimental: KRAS peptide vaccine, Nivolumab, and Ipilimumab
Interventions:
  • Drug: KRAS peptide vaccine
  • Drug: Nivolumab
  • Drug: Ipilimumab
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥18 years.
  • Have histologically or cytologically - proven cancer of the pancreas or microsatellite stable (MSS)-colon.
  • Does not have measurable disease by imaging.
  • Have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping.
  • Have one of the six KRAS mutations (KRASG12C, KRASG12V, KRASG12D, KRASG12A, KRASG13D or KRASG12R) in vaccine expressed in tumor.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Life expectancy of greater than 6 months.
  • Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
  • Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
  • Men must use acceptable form of birth control while on study.
  • Ability to understand and willingness to sign a written informed consent document.
  • Last dose of adjuvant chemotherapy or radiation therapy administered within 6 months of screening tests.

Exclusion Criteria

  • If expected to require any other form of systemic or localized antineoplastic therapy while on study.
  • Within 2 weeks prior to first dose of study drug.

    • Any systemic or topical corticosteroids at immunosuppressive agents.
    • Any palliative or adjuvant radiation or gamma knife radiosurgery.
    • Any chemotherapy.
  • Within 4 weeks prior to first dose of study drug.

    • Any investigational cytotoxic drug.
    • Any investigational device.
    • Has received a live vaccine.
    • Received any allergen hyposensitization therapy.
    • Received any growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin.
    • Any major surgery.
  • Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), etc.).
  • Hypersensitivity reaction to any monoclonal antibody.
  • Known history or evidence of brain metastases.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
  • Known history or concurrent interstitial lung disease.
  • Has a pulse oximetry < 92% on room air.
  • Requires the use of home oxygen.
  • Infection with HIV or hepatitis B or C.
  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Has been diagnosed with another cancer or myeloproliferative disorder within the past 5 year.
  • Has a diagnosis of immunodeficiency.
  • Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
  • Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
  • Unwilling or unable to follow the study schedule for any reason.
  • Are pregnant or breastfeeding.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu
Contact: Ellen Lilly-Forman, RN 443-287-4961 lillyel@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04117087
Other Study ID Numbers  ICMJE J1994
IRB00210915 ( Other Identifier: Johns Hopkins Medical Institution )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Nilofer Azad, MD Johns Hopkins Medical Institution
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date October 2019

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