Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome
NCT ID: NCT05419011
Last Updated: 2026-02-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE2
186 participants
INTERVENTIONAL
2023-05-08
2028-01-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients
NCT05078866
A Vaccine (Ad5.F35-hGCC-PADRE) for the Treatment of Gastrointestinal Adenocarcinoma
NCT04111172
Vaccine Therapy in Treating Patients With Colorectal, Stomach, or Pancreatic Cancer
NCT01191684
Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer
NCT00019591
Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma
NCT00085189
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
VII. To compare the number of mismatch repair deficient (MMR-deficient) crypts at baseline to the number of MMR-deficient crypts at the one year post-vaccination colonoscopy both overall and on a per patient basis.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Biopsy Procedure
Undergo biopsy
Biospecimen Collection
Undergo blood sample collection
Colonoscopy
Undergo SOC colonoscopy
Nogapendekin Alfa
Given nogapendekin alfa inbakicept (N-803) SC
Questionnaire Administration
Ancillary studies
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.
Biopsy Procedure
Undergo biopsy
Biospecimen Collection
Undergo blood sample collection
Colonoscopy
Undergo SOC colonoscopy
Placebo Administration
Given SC
Questionnaire Administration
Ancillary studies
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.
Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Biopsy Procedure
Undergo biopsy
Biospecimen Collection
Undergo blood sample collection
Colonoscopy
Undergo SOC colonoscopy
Questionnaire Administration
Ancillary studies
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.
Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Biopsy Procedure
Undergo biopsy
Biospecimen Collection
Undergo blood sample collection
Colonoscopy
Undergo SOC colonoscopy
Nogapendekin Alfa
Given nogapendekin alfa inbakicept (N-803) SC
Questionnaire Administration
Ancillary studies
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Adenovirus 5 CEA/MUC1/Brachyury Vaccine Tri-Ad5
Given SC
Biopsy Procedure
Undergo biopsy
Biospecimen Collection
Undergo blood sample collection
Colonoscopy
Undergo SOC colonoscopy
Nogapendekin Alfa
Given nogapendekin alfa inbakicept (N-803) SC
Placebo Administration
Given SC
Questionnaire Administration
Ancillary studies
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Mutation positive: MLH1, MSH2/EPCAM and MSH6 genotypes with prior history of ≥1 colorectal neoplasms\*\* (tubular or tubulovillous adenoma\[s\] or sessile serrated polyps/adenomas/lesion\[s\] or traditional serrated adenoma\[s\]), and/or colorectal 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)
* Note: Should be confirmed by pathology report or letter from endoscopist to participant
* 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). Ongoing adjuvant endocrine therapy is allowed
* 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 =\< institutional upper limit of normal
* Note: Higher bilirubin levels (\<= 3 mg/dL) can be allowed if due to a known benign liver condition, i.e. Gilbert's
* 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 =\< institutional upper limit of normal or estimated glomerular filtration rate (eGFR) \>= 60 ml/min/1.73m\^2
* 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
* 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
* History of atrial fibrillation
* History of gastrointestinal hemorrhage and intracranial hemorrhage
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Ajay Bansal
Role: PRINCIPAL_INVESTIGATOR
University of Kansas
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
University of Arizona Cancer Center - Prevention Research Clinic
Tucson, Arizona, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
University of Colorado
Denver, Colorado, United States
Northwestern University
Chicago, Illinois, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
M D Anderson Cancer Center
Houston, Texas, United States
University of Puerto Rico
San Juan, , Puerto Rico
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2021-14234
Identifier Type: REGISTRY
Identifier Source: secondary_id
NCI 21-05-01
Identifier Type: -
Identifier Source: secondary_id
NCI21-05-01
Identifier Type: OTHER
Identifier Source: secondary_id
INT21-05-01
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2021-14234
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.