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Trial record 1 of 1 for:    NCT05419011
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Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome

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ClinicalTrials.gov Identifier: NCT05419011
Recruitment Status : Recruiting
First Posted : June 15, 2022
Last Update Posted : February 14, 2024
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase IIb trial tests whether Tri-Ad5 in combination with N-803 works to prevent colon and other cancers in participants with Lynch syndrome. Each of the three injections in Tri-Ad5 vaccine contain a different substance that is in precancer and cancer cells. Injecting these substances may cause the immune system to develop a defense against cancer that recognizes and destroys any precancer and cancer cells that produce these proteins in the future. N-803 may increase immune responses to other vaccines. Giving Tri-Ad5 in combination with immune enhancing N-803 may lower the chance of developing colon and other cancers in participants with Lynch syndrome.

Condition or disease Intervention/treatment Phase
Lynch Syndrome Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5 Procedure: Biopsy Procedure: Biospecimen Collection Procedure: Colonoscopy Drug: Nogapendekin Alfa Drug: Placebo Administration Other: Questionnaire Administration Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 186 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase IIB Clinical Trial of the Multitargeted Recombinant Adenovirus 5 (CEA/MUC1/Brachyury) Vaccine (TRI-AD5) and IL-15 Superagonist N-803 in Lynch Syndrome
Actual Study Start Date : March 22, 2023
Estimated Primary Completion Date : February 1, 2027
Estimated Study Completion Date : February 1, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: Arm I (Tri-Ad5, N-803)
Participants receive Tri-Ad5 SC and N-803 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 and 104 weeks. Participants undergo blood sample collection throughout the study.
Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Other Names:
  • Ad5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
  • Ad5-CEA/Ad5-MUC1/Ad5-Brachyury Vaccine Tri-Ad5
  • Adenoviral CEA/MUC1/Brachyury Vaccine Tri-Ad5
  • Tri Ad5
  • Tri-Ad5
  • TriAd5

Procedure: Biopsy
Undergo biopsy
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Procedure: Colonoscopy
Undergo SOC colonoscopy

Drug: Nogapendekin Alfa
Given nogapendekin alfa inbakicept (N-803) SC
Other Names:
  • ALT 803
  • ALT-803
  • ALT803
  • Fusion Protein Consisting of IL-15N72D and IL-15RaSu/FC
  • IL-15N72D/IL-15Ra-Fc
  • IL-15N72D:IL-15RaSu/Fc Fusion Complex
  • N 803
  • N-803
  • N803
  • Superagonist Interleukin-15:Interleukin-15 Receptor AlphaSu/Fc Fusion Complex Alt-803

Other: Questionnaire Administration
Ancillary studies

Placebo Comparator: Arm II (placebo)
Participants receive placebo SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 and 104 weeks. Participants undergo blood sample collection throughout the study.
Procedure: Biopsy
Undergo biopsy
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Procedure: Colonoscopy
Undergo SOC colonoscopy

Drug: Placebo Administration
Given SC

Other: Questionnaire Administration
Ancillary studies

Experimental: Safety phase I (Tri-Ad5)
Participants receive Tri-Ad5 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 weeks and 104 weeks. Participants undergo blood sample collection throughout the study.
Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Other Names:
  • Ad5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
  • Ad5-CEA/Ad5-MUC1/Ad5-Brachyury Vaccine Tri-Ad5
  • Adenoviral CEA/MUC1/Brachyury Vaccine Tri-Ad5
  • Tri Ad5
  • Tri-Ad5
  • TriAd5

Procedure: Biopsy
Undergo biopsy
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Procedure: Colonoscopy
Undergo SOC colonoscopy

Other: Questionnaire Administration
Ancillary studies

Experimental: Safety phase II (Tri-Ad5 , N-803)
Participants receive Tri-Ad5 SC and N-803 SC at weeks 0, 4, 8, and 52. Participants also undergo SOC colonoscopy with biopsy at baseline and at 52 weeks and 104 weeks. Participants undergo blood sample collection throughout the study.
Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Other Names:
  • Ad5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
  • Ad5-CEA/Ad5-MUC1/Ad5-Brachyury Vaccine Tri-Ad5
  • Adenoviral CEA/MUC1/Brachyury Vaccine Tri-Ad5
  • Tri Ad5
  • Tri-Ad5
  • TriAd5

Procedure: Biopsy
Undergo biopsy
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Procedure: Colonoscopy
Undergo SOC colonoscopy

Drug: Nogapendekin Alfa
Given nogapendekin alfa inbakicept (N-803) SC
Other Names:
  • ALT 803
  • ALT-803
  • ALT803
  • Fusion Protein Consisting of IL-15N72D and IL-15RaSu/FC
  • IL-15N72D/IL-15Ra-Fc
  • IL-15N72D:IL-15RaSu/Fc Fusion Complex
  • N 803
  • N-803
  • N803
  • Superagonist Interleukin-15:Interleukin-15 Receptor AlphaSu/Fc Fusion Complex Alt-803

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Cumulative incidence rate of the composite endpoint of adenomas (tubular, tubulovillous and serrated), advanced adenomas and colon cancer [ Time Frame: At 104 weeks ]
    Will be compared between the two arms using a stratified Cochran-Mantel-Haenszel test where the randomization stratification factors will be included as strata. The cumulative events rates will be reported for each study arm along with the corresponding two-sided 95% confidence intervals.


Secondary Outcome Measures :
  1. Association of clinical factors with immune responses [ Time Frame: At 104 weeks ]
    Will be evaluated by conducting univariate and multivariate binary regression analyses. These analyses will be conducted for both arms combined (in which case arm is included as a stratification factor in the model) and each arm separately. The proportions of cells within adenomas expressing stem cells markers pre- and post-vaccination will be compared within each study arm using the signed rank test, and within-subject changes will be compared between responders and non-responders using Wilcoxon rank-sum test for each arm separately and both arms combined. Comparisons between study arms will be conducted using a Wilcoxon rank-sum test.

  2. Incidence of extracolonic neoplasms [ Time Frame: At 104 weeks ]
    Will compare the observed incidences of lynch syndrome (LS)-related extracolonic cancers to historical control incidence of LS-related extracolonic cancers in this patient population. We will collect the information about extracolonic cancers by asking the participants and by reviewing the pathology reports for confirmation.


Other Outcome Measures:
  1. Number of antigen-specific T-cells, peripheral blood mononuclear cells (PBMCs), serum soluble factors and antibody levels [ Time Frame: At baseline, 12 weeks, and 56 weeks ]
    Will be log-transformed before conducting any analyses. Comparisons of number of antigen-specific T-cells, PBMCs, serum soluble factors and antibodies between study arms will be conducted using a nonparametric Wilcoxon rank sum test. IgG titers that will be measured serially will be analyzed and compared between the two arms using linear mixed effects models. If zero-inflation is detected, generalized linear mixed models with zero-inflated Poisson or negative binomial distributions will be fitted.

  2. Prevalence of immune cells markers, tumor associated antigens and stem cell markers [ Time Frame: At baseline, 52 weeks, and 104 weeks ]
    Will be reported using repeated measures techniques. We will also compare pre- and post-vaccination size, number and histology of polyps.

  3. Differential expression analyses [ Time Frame: At baseline, 52 weeks, and 104 weeks ]
    Will be using Bioconductor R package DESeq2. A paired sample design to compare post- to pre-vaccination samples within each study arm and for both arms combined. Significant genes with Benjamini-Hochberg-adjusted p-value =< 0.05 and absolute value of log2-fold change >= 0.5 will be annotated with pathways of interest in volcano plots.

  4. Immune cell gene enrichment analysis [ Time Frame: At baseline, 52 weeks, and 104 weeks ]
    Will be calculated using raw read counts with Bioconductor R package GSVA.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Participants with LS defined as one of the following:

    • Mutation positive: MLH1, MSH2/EPCAM and MSH6 genotypes with prior history of >= 1 adenoma(s) and/or >= 1 advanced adenoma(s) and/or colon cancer(s) (but no active cancer for 6 months) OR
    • PMS2 genotype with prior history of colon cancer(s) (but no active cancer for 6 months)
  • Participants must have at least part of the descending/sigmoid colon and/or rectum intact
  • Participants must be at least 6 months from any cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy or radiation)
  • Participants >= 18 years will be enrolled. Because the risk of LS related cancers is very low in participants < 18 years of age, children and adolescents are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/microliter
  • Absolute neutrophil count >= 1,500/microliter
  • Platelets >= 100,000/microliter
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits
  • The effects of the Tri-Ad5 vaccines and N-803 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Participants must be willing and able to space coronavirus disease (COVID) vaccines at least 2 weeks prior to and 2 weeks after receipt of study agent

Exclusion Criteria:

  • History of organ allograft or other history of immunodeficiency
  • Known human immunodeficiency virus (HIV) with CD4 count < 540, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection will be permitted. Poorly controlled HIV may prevent an adequate immune response to the vaccine and will be an exclusion criterion
  • Subjects requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 3 months of vaccination
  • Participants may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to adenovirus-based vaccines and N-803
  • Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because of the unknown effects of the vaccine and N-803 on the fetus. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with the vaccine plus N-803, breastfeeding should be discontinued if the mother is treated with the vaccine plus N-803
  • History of untreated thrombotic disorders
  • Participants who experienced severe side effects or allergic reactions to previous adenovirus-based vaccines (such as Johnson and Johnson COVID vaccine) will be excluded

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): NCT05419011


Locations
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United States, Arizona
Mayo Clinic Hospital in Arizona Not yet recruiting
Phoenix, Arizona, United States, 85054
Contact: Niloy J. Samadder    480-342-6263    Samadder.jewel@mayo.edu   
Principal Investigator: Niloy J. Samadder         
University of Arizona Cancer Center - Prevention Research Clinic Recruiting
Tucson, Arizona, United States, 85719
Contact: Aaron J. Scott    520-626-6453    ajscott@arizona.edu   
Principal Investigator: Aaron J. Scott         
United States, California
UCSF Medical Center-Parnassus Not yet recruiting
San Francisco, California, United States, 94143
Contact: Aparajita Singh    415-502-4444    Aparajita.singh@ucsf.edu   
Principal Investigator: Aparajita Singh         
United States, Colorado
University of Colorado Not yet recruiting
Denver, Colorado, United States, 80217-3364
Contact: Swati G. Patel    720-848-2777    swati.patel@cuanschutz.edu   
Principal Investigator: Swati G. Patel         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Mohammad A. Abbass    312-694-4789    Mohammad.Abbass@nm.org   
Principal Investigator: Mohammad A. Abbass         
United States, Kansas
University of Kansas Cancer Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Ajay Bansal    913-588-6003    abansal@kumc.edu   
Principal Investigator: Ajay Bansal         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Ramona M. Lim    617-582-7777    ColonScreening@DFCI.harvard.edu   
Principal Investigator: Ramona M. Lim         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Elena M. Stoffel    734-936-0781    estoffel@med.umich.edu   
Principal Investigator: Elena M. Stoffel         
United States, Minnesota
Mayo Clinic in Rochester Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Lisa A. Boardman    507-266-4388    boardman.lisa@mayo.edu   
Principal Investigator: Lisa A. Boardman         
United States, Ohio
Cleveland Clinic Foundation Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Carol A. Burke    216-444-6864    BURKEC1@ccf.org   
Principal Investigator: Carol A. Burke         
Ohio State University Comprehensive Cancer Center Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Peter P. Stanich    614-293-6255    peter.stanich@osumc.edu   
Principal Investigator: Peter P. Stanich         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Eduardo Vilar-Sanchez    713-563-4743    EVilar@mdanderson.org   
Principal Investigator: Eduardo Vilar-Sanchez         
United States, Utah
Huntsman Cancer Institute/University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84112
Contact: Joanne M. Jeter    801-646-4007    joanne.jeter@hci.utah.edu   
Principal Investigator: Joanne M. Jeter         
Puerto Rico
University of Puerto Rico Not yet recruiting
San Juan, Puerto Rico, 00936
Contact: Marcia R. Cruz-Correa    787-772-8300    marcia.cruz1@upr.edu   
Principal Investigator: Marcia R. Cruz-Correa         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ajay Bansal University of Kansas
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05419011    
Other Study ID Numbers: NCI-2021-14234
NCI-2021-14234 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI 21-05-01
NCI21-05-01 ( Other Identifier: Northwestern University )
INT21-05-01 ( Other Identifier: DCP )
P30CA060553 ( U.S. NIH Grant/Contract )
UG1CA242596 ( U.S. NIH Grant/Contract )
UG1CA242609 ( U.S. NIH Grant/Contract )
UG1CA242632 ( U.S. NIH Grant/Contract )
UG1CA242635 ( U.S. NIH Grant/Contract )
UG1CA242643 ( U.S. NIH Grant/Contract )
First Posted: June 15, 2022    Key Record Dates
Last Update Posted: February 14, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 'NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page'
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms, Hereditary Nonpolyposis
Syndrome
Disease
Pathologic Processes
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs