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 : May 9, 2024
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Tracking Information | |||||||
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First Submitted Date ICMJE | June 14, 2022 | ||||||
First Posted Date ICMJE | June 15, 2022 | ||||||
Last Update Posted Date | May 9, 2024 | ||||||
Actual Study Start Date ICMJE | May 8, 2023 | ||||||
Estimated Primary Completion Date | February 1, 2027 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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.
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Original Primary Outcome Measures ICMJE |
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 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.
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Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | |||||||
Brief Title ICMJE | Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome | ||||||
Official Title ICMJE | 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 | ||||||
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. | ||||||
Detailed Description | PRIMARY OBJECTIVE: I. To evaluate if the combination of trivalent adenovirus-5 (Tri-Ad5) vaccines and IL-15 superagonist nogapendekin alfa inbakicept (N-803) reduces the incidence of colorectal neoplasms in patients with Lynch syndrome (LS). SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of the Tri-Ad5 vaccines + N-803 in combination. II. To correlate clinical factors such as use of aspirin and non-steroidal anti-inflammatory drugs (NSAID), smoking and alcohol intake with immune responses. III. To evaluate the effect of Tri-Ad5 vaccines on the incidence of LS-related extracolonic cancers. IV. To systematically measure the participants' behavior and experience in terms of vaccine uptake, cancer-specific distress and quality of life. EXPLORATORY OBJECTIVES: I. To determine the ability of the Tri-Ad5 vaccines + N-803 to generate a 2-fold increase in T cell responses (cell-mediated immunity) at week 12 (early immune response) and at week 56 (long-term memory response). II. To evaluate circulating anti-MUC1 IgG (antibody-mediated immunity) after Tri-Ad5 vaccines + N-803. III. To compare the expression of the three tumor associated antigen (TAAs): MUC1, carcinoembryonic antigen (CEA) and brachyury in colorectal neoplasms before and after Tri-Ad5 vaccines + N-803. IV. To evaluate changes in the immune profile and abundance of resident immune cell types in colonic mucosa after vaccination with Tri-Ad5 vaccines + N-803 using messenger ribonucleic acid sequencing (mRNAseq) and immunohistochemistry (IHC). V. To test the effects of the vaccines alone or in combination with N-803 on specific immune subsets of peripheral blood mononuclear cells (PBMCs) and serum soluble factors and cytokines. VI. To compare the expression of stem cell markers in colorectal neoplasms before and after Tri-Ad5 vaccines + N-803. OUTLINE: SAFETY PHASE I: Participants receive Tri-Ad5 subcutaneously (SC) at weeks 0, 4, 8, and 52. Participants also undergo standard of care (SOC) colonoscopy with biopsy at baseline, at 52 weeks and 104 weeks. SAFETY PHASE II: 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, 52 weeks and 104 weeks. RANDOMIZED CONTROL PHASE: Participants are randomized into 1 of two arms. ARM I: 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. ARM II: 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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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Prevention |
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Condition ICMJE | Lynch Syndrome | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
186 | ||||||
Original Estimated Enrollment ICMJE |
158 | ||||||
Estimated Study Completion Date ICMJE | February 1, 2027 | ||||||
Estimated Primary Completion Date | February 1, 2027 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | |||||||
Listed Location Countries ICMJE | Puerto Rico, United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT05419011 | ||||||
Other Study ID Numbers ICMJE | 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 ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | National Cancer Institute (NCI) | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||||
Verification Date | April 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |