Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome
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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05419011 |
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Recruitment Status :
Recruiting
First Posted : June 15, 2022
Last Update Posted : April 17, 2024
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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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 |
Show detailed description
| 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 : | May 8, 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 Genetics related topics:
Lynch syndrome
MedlinePlus related topics:
Vaccines
| Arm | Intervention/treatment |
|---|---|
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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.
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Biological: Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Other Names:
Procedure: Biopsy Undergo biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Procedure: Colonoscopy Undergo SOC colonoscopy Drug: Nogapendekin Alfa Given nogapendekin alfa inbakicept (N-803) SC
Other Names:
Other: Questionnaire Administration Ancillary studies |
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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.
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Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
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:
Procedure: Biopsy Undergo biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
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:
Procedure: Biopsy Undergo biopsy
Other Names:
Procedure: Biospecimen Collection Undergo blood sample collection
Other Names:
Procedure: Colonoscopy Undergo SOC colonoscopy Drug: Nogapendekin Alfa Given nogapendekin alfa inbakicept (N-803) SC
Other Names:
Other: Questionnaire Administration Ancillary studies |
Primary Outcome Measures :
- 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 :
- 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.
- 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:
- 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.
- 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.
- 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.
- 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
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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:
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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
| 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 | 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
| Principal Investigator: | Ajay Bansal | University of Kansas |
| 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: | April 17, 2024 |
| Last Verified: | April 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 |
| 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 |