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Pilot Study of Neoantigen Peptides for the Treatment of Neoplasms

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: NCT04509167
Recruitment Status : Enrolling by invitation
First Posted : August 11, 2020
Last Update Posted : September 10, 2020
Sponsor:
Information provided by (Responsible Party):
Instituto de Medicina Regenerativa

Brief Summary:
This research is a pilot clinical trial using personalized neoantigen peptide vaccines with an adjuvant (Montanide ISA-51 VG), in patients with different types of cancer

Condition or disease Intervention/treatment Phase
Neoplasms Biological: Neoantigen Peptides Early Phase 1

Detailed Description:

Rationale: Cancer cells express unique peptide antigens recognized by CD8+ cytotoxic T lymphocytes (CTL), which are typically 8-10 amino acids long and are presented in association with Class I MHC molecules. The peptides recognized by helper (CD4+) T-cells are presented in association with Class II MHC molecules and are usually longer (13-18 amino acids in length), although peptide elution studies have indicated no apparent restriction on peptide length. Selected peptides can induce circulating T cell responses in most patients, and that vaccination with a mixture of peptides is immunogenic in up to 100% of patients. The magnitude of T cell responses sometimes is substantial, with 1-5% of circulating CD8 T cells reactive to single antigens. T cell responses to vaccines may be durable for months or years, but are at least as likely to be transient, sometimes declining even while still receiving vaccines. However, T cells induced by vaccination can recognize and lyse cancerous cells expressing the relevant protein and MHC, and peptide vaccines induce promising immunogenicity.

Though MHC-restriction of individual peptides limits their use to a subset of patients, there are mixtures of a dozen peptides restricted by HLA-A1, A2, A3, or A11 can be prepared as a stable mixture and can induce immune responses in 85% of patients with cancer who express one or more of those MHC molecules, without negative effects from competition among the peptides. Other experience supports the ability to induce T cell responses to multiple peptides when vaccinating with peptide mixtures. Since antigenic peptides are easily degraded by proteases in the body, it is difficult for the receptors expressed on the immune cells to identify antigen epitopes, and they do not generate a strong immune response to pathogens. An epitope-based vaccine with a reasonable design is composed of epitope peptide/s, a delivery system, and an adjuvant. For multi-epitope vaccines, since the traditional carriers and adjuvants are associated with poor efficacy, vaccine designs with built-in adjuvants have been proposed. Therefore, a built-in adjuvant exhibiting both the functions of a transmission system and a traditional adjuvant, is constructed within the vaccine to improve the immunogenicity of epitope peptides by stimulating the innate immune response required for an adaptive immune response. To achieve this goal, the epitopes are regularly fused with adjuvant proteins or displayed on the surface of some particular biomaterials (e.g., liposomes, gold nanoparticles, and poly(lactic-co-glycolic acid) (PLGA)) and the immunogenicity of the epitopes are significantly increased by this immune complex.

Study design: This research is a pilot clinical trial using a personalized neoantigen peptide vaccine. Approximately 100 patients with cancer and whose sequencing studies show the presence of neoantigens will receive the personalized multi-peptide vaccine. Peptide vaccines will be given with an adjuvant (Montanide ISA-51 VG) by intradermal injection (~0.5 mg of each peptide) in the arm every week for a maximum of 8 weeks; the treatment will be discontinued if disease progresses or if there is deterioration of the patient's general condition. All patients will give written informed consent; their data will be coded and fully anonymized. The study was approved by the Ethics Committee of the Regenerative Medicine Institute and conformed to the ethical guidelines of the Declaration of Helsinki.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Personalized Neoantigen Peptide Vaccines for the Treatment of Neoplasms
Actual Study Start Date : August 10, 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : August 2021

Arm Intervention/treatment
Experimental: Treatment
Patients will receive intradermal injection of individualized neoantigen peptides vaccine at a dose of ~500ug per peptide once a week for 8 weeks.
Biological: Neoantigen Peptides
Patients will receive intradermal injection of individualized neoantigen peptides vaccine at a dose of ~500ug per peptide once a week for 8 weeks.




Primary Outcome Measures :
  1. Change from Baseline in WBC count at 2, 6, 12 months [ Time Frame: Baseline, 2, 6, 12 months ]
    WBC quantification in blood and comparison at different timepoints

  2. Change from Baseline in RBC count at 2, 6, 12 months [ Time Frame: Baseline, 2, 6, 12 months ]
    RBC quantification in blood and comparison at different timepoints


Secondary Outcome Measures :
  1. Change from Baseline in Calcitonin levels at 2, 6, 12 months [ Time Frame: Baseline, 2, 6, 12 months ]
    Measured in blood, to assess treatment response at different timepoints

  2. Change from Baseline in CA-125 levels at 2, 6, 12 months [ Time Frame: Baseline, 2, 6, 12 months ]
    Measured in blood, to assess treatment response at different timepoints

  3. Change from Baseline in beta-2-microglobulin levels at 2, 6, 12 months [ Time Frame: Baseline, 2, 6, 12 months ]
    Measured in blood and urine, to assess treatment response at different timepoints

  4. Change from Baseline in sum of diameter of target lesions at 2, 6, 12 months [ Time Frame: Baseline, 2, 6, 12 months ]
    Measured in the longest diameter in the plane of measurement in CT according to RECIST 1.1 criteria

  5. Change from Baseline in sum of diameter of non-target lesions at 2, 6, 12 months [ Time Frame: Baseline, 2, 6, 12 months ]
    Measured in the longest diameter in the plane of measurement in CT according to RECIST 1.1 criteria



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 16 years of age or older, male or female
  • Life expectancy of at least 3 months
  • Confirmed tumor by imaging studies
  • Have adequate organ function, as measured by laboratory values: Lymphocyte ratio >20%; WBC >3.0×10^9/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; if the patient has liver metastases, ALT and AST ≤5 × ULN; Alkaline phosphatase (ALP)≤2.5 × ULN; total serum bilirubin (TBIL) < 1.5 × ULN; Urea nitrogen (BUN)≤1.5 × ULN; Creatinine (Cr)1.5≤ULN; Normal blood coagulation function, urine routine, and electrocardiogram (ECG)
  • Available tumor specimen for sequencing and neoantigen determination
  • Ability to find 3 or more neoantigen epitopes
  • Ability to follow research and follow-up procedures
  • Able to understand and willing to sign an IRB approved written informed consent document
  • Agree with the use of contraception or partner of child-bearing potential agrees to use adequate contraception which will include two of the following: hormonal or barrier method of birth control, or abstinence prior to study entry, for the duration of study participation, and for 30 days following completion of therapy

Exclusion Criteria:

  • History of immunodeficiency disorder or autoimmune condition requiring active immunosuppressive therapy
  • Evidence of Liver and kidney dysfunction, severe heart disease, or coagulation dysfunction
  • Known diagnosis of an infectious condition including hepatitis, HIV, CMV, and Treponema pallidum
  • Participant becomes pregnant and/or is breastfeeding or plans on becoming pregnant during study
  • A psychiatric illness that would limit compliance with study requirements as determined by the investigator or the investigator believes that participant is not suitable for inclusion

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): NCT04509167


Locations
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Mexico
Instituto de Medicina Regenerativa
Tijuana, Baja California, Mexico, 22100
Sponsors and Collaborators
Instituto de Medicina Regenerativa
Investigators
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Principal Investigator: Jesus Perez, MD Instituto de Medicina Regenerativa
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Responsible Party: Instituto de Medicina Regenerativa
ClinicalTrials.gov Identifier: NCT04509167    
Other Study ID Numbers: PEP-NEO-001
First Posted: August 11, 2020    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Instituto de Medicina Regenerativa:
tumor
cancer
Additional relevant MeSH terms:
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Neoplasms