Pancreatic Ductal AdenocarcinomaPhase 2NCT04111172
A Vaccine (Ad5.F35-hGCC-PADRE) for the Treatment of Gastrointestinal Adenocarcinoma
A Phase 2 study testing Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE in people with Pancreatic Ductal Adenocarcinoma and Colorectal Adenocarcinoma, run by Thomas Jefferson University at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn whether the Ad5.F35-hGCC-PADRE vaccine is safe and can stimulate an immune response against gastrointestinal (GI) cancers in patients with pancreatic, colorectal, esophageal, gastric, or small bowel adenocarcinomas who have completed surgical resection and standard adjuvant… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Ductal Adenocarcinoma, Colorectal Adenocarcinoma, Gastric Adenocarcinoma
- What is being tested?
- Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2020to Apr 2028
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study:
- 1. Males or females aged ≥ 18 years 2. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 3. Subjects with tumors specified below, who are at high risk of relapse, have been treated with curative intent, and have no evidence of disease (NED) following front-line therapy with surgery, radiation therapy, and/or chemotherapy. NED includes, where applicable, surgical (macroscopic tumor margin, at the time of surgery), and radiological evidence of disease. Residual lesions identified by microscopic/frozen margins and biochemical markers are permitted. Therapy must have been completed no fewer than four weeks, and no later than 25 weeks, before the first dose of Ad5.F35-hGCC-PADRE. For expansion cohort (2B), colon cancer patients may be enrolled four weeks after completion of standard adjuvant therapies, however there is no upper limit to enrollment as long as patients fulfil other eligibility requirements are ctDNA+.
- 4. For tumor-specific criteria, please refer to the information below:
- Pancreatic ductal adenocarcinoma i. Stage I, II, III
- Neuroendocrine tumors of the pancreas are not permitted b. Colorectal adenocarcinoma i. Stage III; Stage IV following metastasectomy ii. High risk stage II colon cancer defined as (any of):
- T4
Show all 25Show fewer
- Grade ≥ 3
- Clinical presentation with bowel obstruction or perforation
- Histological signs of vascular, lymphatic or perineural invasion
- < 12 lymph nodes examined c. Gastric adenocarcinoma i. Stage IIA, IIB, III
- Gastrointestinal stromal tumors of the stomach are not permitted d. Esophageal adenocarcinoma i. Stage IIB, III
- Esophageal squamous cell carcinomas are not permitted e. Small bowel adenocarcinomas i. Stage III ii. High risk stage II defined as (any of):
- T4
- Grade ≥ 3
- Clinical presentation with perforation or bowel obstruction
- Histological signs of vascular, lymphatic or perineural invasion
- <5 lymph nodes for duodenal or <8 lymph nodes for jejunal/ ileal tumor location 5. Have an anticipated life expectancy of greater than 12 weeks 6. Have adequate organ function at screening
- ANC ≥ 1000 cells/mL
- Platelets ≥ 75,000 /mL
- Hemoglobin ≥ 9.0 g/dL
- Serum creatinine < 2.0 mg/dL
- For other blood and urine tests including blood chemistry, hepatic and renal functions, test results should not be worse than Grade 1 levels of abnormalities defined by CTCAE, NCI version 5 issued by the US Department of Health and Human Services.
- 7. For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormonal implants) or abstinence must be used throughout the study period and for 28 days after their final vaccine administration (A barrier method of contraception must be employed by all subjects [male and female], regardless of other methods unless abstinent). A negative serum or urine pregnancy test is required as part of screening.
- Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/ml.
- 8. Be willing to comply with all the study procedures. 9. All subjects must be able to comprehend and sign a written informed consent document 10. For expansion cohort (2B) only, colon cancer patients must be ctDNA positive using CLIA-certified commercially available assays obtained as part of standard of care.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Have a known history or evidence of residual disease after definitive surgery
- Have a known metastasis in the brain or central nervous system
- Have a history of splenectomy
- Have a history of distal pancreatectomy
- Concurrent use of systemic steroids or immunosuppressive drugs (use of topical or inhaled steroids will be allowed, see Section 5.7)
Show all 21Show fewer
- Have any immunodeficiency disease or immunocompromised state (e.g., use of immunosuppressive agents, chemotherapy or radiation therapy within four weeks of study treatment)
- Have active autoimmune disease or history of autoimmune disease or a transplant recipient requiring systemic steroids or other immunosuppressive treatment
- Have received a diagnosis of HIV, hepatitis B, or hepatitis C (subjects who are hepatitis C positive may be enrolled if they are confirmed with negative viral load at screening)
- Other malignancy within last 5 years except curatively treated non-melanomatous skin cancer and curatively treated carcinoma in situ of the uterine cervix, or early-stage (stage A or B1) prostate cancer
- Have a history of inflammatory bowel disease
- Have a history of serious reaction to adenovirus
- Have an intercurrent illness that is either life-threatening or of clinical importance such that it might limit study compliance (such illnesses include, but are not limited to, ongoing or active infection, metabolic or neurologic disease, peripheral vascular disease, or psychiatric illness)
- Have insufficient peripheral venous access to permit completion of the study phlebotomy regimen
- Consumes greater than three glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day and cannot refrain from alcohol for the duration of the trial
- Has a history of use of illicit drugs (e.g., opioids, cocaine, amphetamines, hallucinogens, etc.) that could potentially interfere with adherence to study procedures or requirements
- Be a woman who is pregnant or breastfeeding
- Have an unhealed surgical wound
- Have had major surgery or significant traumatic injury occurring within 28 days before treatment or anticipated surgery or procedure requiring general anesthesia during the study participation (including four weeks after last dose of vaccine).
- Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy
- Patients are currently enrolled in an ongoing clinical trial or trial that could interfere with the protocol-specified requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Phase 2A/2B, Dose-Finding and Expansion Study of Ad5.F35-hGCC-PADRE Vaccine in Adults With Gastrointestinal Adenocarcinomas at Risk of Relapse Post Definitive Surgery and Standard Therapy
The goal of this clinical trial is to learn whether the Ad5.F35-hGCC-PADRE vaccine is safe and can stimulate an immune response against gastrointestinal (GI) cancers in patients with pancreatic, colorectal, esophageal, gastric, or small bowel adenocarcinomas who have completed surgical resection and standard adjuvant therapy. An additional goal is to evaluate whether the vaccine may help eliminate minimal residual disease (MRD) in ctDNA-positive colon cancer patients.
The main questions it aims to answer are:
Read more
Is the Ad5.F35-hGCC-PADRE vaccine safe and tolerable at different dose levels? Does the vaccine induce GCC-specific T-cell immune responses in patients with GI malignancies? In ctDNA-positive colon cancer patients, can the vaccine promote ctDNA clearance as a marker of MRD elimination?
The investigators will compare immune responses across different vaccine dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) to determine the optimal dose.
Participants will:
Receive the Ad5.F35-hGCC-PADRE vaccine by intramuscular injection. Be assigned to one of three dose levels during the dose-finding phase or receive a prespecified dose in the dose-expansion cohort.
Undergo safety assessments, including monitoring for adverse events, injection-site reactions, and laboratory test abnormalities.
Have blood samples collected to evaluate GCC-specific T-cell immune responses. For ctDNA-positive colon cancer patients, undergo ctDNA testing to assess clearance of minimal residual disease.
Read the detailed description
This is an open-label, dose-finding, single-center, study of Ad5.F35-hGCC-PADRE vaccine delivered intramuscularly in subjects with colorectal, pancreatic, gastric, esophageal, or small bowel cancers who are at high risk of relapse without evidence of disease post definitive surgery and standard therapy.
Study treatment will start after surgery and standard therapy. Subjects who meet the eligibility criteria can participate in this study at least four and no more than 24 weeks ± one week post-completion of standard treatment, after they have recovered from the side effects from previous therapies.
Eligible subjects will be sequentially randomized into three treatment arms of 10¹¹, 10¹², and 5 × 10¹² virus particles Ad5.F35-hGCC-PADRE administered by IM injection once every four weeks (± one week) for a total of three administrations. An initial safety lead-in group of 9 subjects (3 in each group) will be randomized sequentially and further enrollment will be paused until they have completed 4 weeks of follow-up to ensure no dose-limiting toxicities (DLT). Moreover, the enrollment of the first 3 subjects will be staggered by an interval of 3 weeks to monitor for acute and subacute toxicities.
Following the completion of assessment of the initial safety lead-in group, a meeting will be held with the PI and the TJU Medical Monitor to review the safety information. If no excessive rates of DLT are observed, enrollment will continue in each dosing arm with continuous monitoring of adverse events. A total of 27 subjects are planned to be randomized to each treatment arm. If it is determined safe to continue enrollment in each dosing arm, a formal letter from the Medical Monitor will be issued.
After 15 patients in each cohort have completed treatment, a futility analysis will be conducted, and information will be informally reviewed with the Medical Monitor.
In the expansion cohort, subjects with colon cancer who meet eligibility criteria will be enrolled after completing surgery and standard of care adjuvant chemotherapy. There is no limit to the amount of time since completing adjuvant therapies to enroll on this cohort. Subjects who are ctDNA+ by CLIA-certified standard of care assay and fulfil other eligibility criteria can enroll at any point post adjuvant therapies. Subjects will receive single IM vaccination with Ad5.F35-hGCC-PADRE at 5 × 10¹² vp. This dose is selected based upon preliminary efficacy data from first part of this study. Patients will be monitored for adverse events over the course of four weeks. Labs will be collected for immunomonitoring and ctDNA will be collected immediately prior to vaccination, at 4 weeks, 12 weeks and up to 52 weeks post-vaccination. Standard of care ctDNA assessments performed post-vaccination will be collected. Optional research blood samples will be collected for patients who opt in and will be collected every 3 months for up to 24 months or until disease recurrence or death whichever comes first.
PRIMARY OBJECTIVES:
- Evaluate the safety and tolerability of sequential Ad5.F35-hGCC-PADRE vaccine administration, delivered intramuscularly (IM) at three dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) four weeks apart in subjects with high-risk colorectal, pancreatic, gastric, esophageal, or small bowel adenocarcinomas with no evidence of disease after surgery and standard therapy.
- For Cohort 2B, evaluate the safety and tolerability of single Ad5.F35-hGCC-PADRE vaccine at 5 × 10¹² vp dose level in MRD+ colon cancer patients with no evidence of radiographic disease
- Evaluate the cellular (T-cell) responses to Ad5.F35-hGCCPADRE at three different dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) administered intramuscularly (IM) as three sequential doses four weeks apart in subjects with high-risk colorectal, pancreatic, gastric, esophageal, or small bowel adenocarcinomas with no evidence of disease after surgery and standard therapy.
- For cohort 2B, evaluate the cellular (T-cell) responses to Ad5.F35-hGCC-PADRE vaccine at 5 × 10¹² vp dose administered IM as one dose in subjects with MRD+ colon cancer with no evidence of radiographic disease after surgery and standard therapy.
EXPLORATORY OBJECTIVES:
- Evaluate the humoral (antibody) responses to Ad5.F35-hGCC-PADRE at three different dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) administered IM as three sequential doses four weeks apart in subjects with high-risk colorectal, pancreatic, gastric, esophageal, or small bowel adenocarcinomas with no evidence of disease after surgery and standard therapy
- Evaluate the association of neutralizing antibodies to Ad5 with immunologic response
- Evaluate the correlation of the immune response to the GCC protein expression in tumors to assess immune tolerance
- Evaluate disease-free survival (DFS)
- Evaluate overall survival (OS), where feasible
- Evaluate the circulatory tumor DNA (ctDNA) status and correlation with clinical recurrence, where feasible
- Evaluate the ctDNA dynamics after single dose of 5 × 10¹² vp Ad5.F35-hGCC-PADRE vaccine in an expansion cohort of ctDNA+ colon cancer patients
- Conditions
- Pancreatic Ductal Adenocarcinoma, Colorectal Adenocarcinoma, Gastric Adenocarcinoma, Clinical Stage II Gastric Cancer AJCC v8, Clinical Stage IIA Gastric Cancer AJCC v8, Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8
- Being tested
- Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE
- Keywords
- circulating tumor DNA, Guanylyl cyclase C, GCC, GUCY2C, ctDNA
- Medical subject headings
- Pancreatic Neoplasms, Colorectal Neoplasms, Gastrointestinal Neoplasms, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adenovirus 5/F35-Human Guanylyl Cyclase C-PADREBiological
Also called Ad5.F35-hGCC-PADRE, Ad5/F35-hGCC-PADRE, Adenovirus 5/F35-HGCC-PADRE
Given as intramuscular injection
| Study group | Role | What they receive |
|---|---|---|
| Arm A (low dose) | Experimental | Patients receive low dose Ad5.F35-hGCC-PADRE vaccine IM on day 1 of weeks 1, 5, and 9 in the absence of disease progression or unacceptable toxicity. Receives: Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE |
| Arm B (medium dose) | Experimental | Patients receive medium dose Ad5.F35-hGCC-PADRE vaccine IM on day 1 of weeks 1, 5, and 9 in the absence of disease progression or unacceptable toxicity. Receives: Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE |
| Arm C (high dose) | Experimental | Patients receive high dose Ad5.F35-hGCC-PADRE vaccine IM on day 1 of weeks 1, 5, and 9 in the absence of disease progression or unacceptable toxicity. Receives: Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE |
| Cohort 2B/Expansion Cohort--ctDNA+ Colon Cancer | Experimental | A group of 20 colon cancer patients who are ctDNA+ by CLIA-certified standard of care assays will receive a single administration of Ad5.F35-hGCC-PADRE vaccine intramuscularly at prespecified dose of 5 × 10¹² vp. Subjects will be followed for the duration of the study until all subjects have reached at least 24 months of follow-up or death. Receives: Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Treatment-Emergent Adverse Events (Phase 2A)
The percentage of subjects with AEs and DLTs will be summarized along with corresponding 95% confidence intervals for each treatment arm and overall. Within each treatment arm, with 24 patients per cohort, if no AEs are observed, the exact 95% confidence interval extends from 0 to 0.14. If one AE is observed, the exact 95% CI extends from 0.001 to 0.21.
Measured: Up to 13 weeks
Percentage of Participants with Treatment-Emergent Adverse Events (Phase 2B)
The percentage of subjects with AEs and DLTs will be summarized along with corresponding 95% confidence intervals for each treatment arm and overall. Within each treatment arm, with 24 patients per cohort, if no AEs are observed, the exact 95% confidence interval extends from 0 to 0.14. If one AE is observed, the exact 95% CI extends from 0.001 to 0.21.
Measured: Up to 5 weeks
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2A)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. the immune parameters will be summarized via percentages of responders and mean/median values, along with corresponding 95% confidence intervals, by treatment arm and measurement time. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For this study, a statistically significant increase in GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline will be considered a response at that time. Significance of the change from baseline will be assessed using the modified distribution-free resampling (DFR) method.
Measured: Baseline to Week 5
Percentage of Participants with a Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2A)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals.
Measured: Baseline to Week 5
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 9 (Phase 2A)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. the immune parameters will be summarized via percentages of responders and mean/median values, along with corresponding 95% confidence intervals, by treatment arm and measurement time. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For this study, a statistically significant increase in GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline will be considered a response at that time. Significance of the change from baseline will be assessed using the modified distribution-free resampling (DFR) method.
Measured: Baseline to Week 9
Percentage of Participants with a Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 9 (Phase 2A)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals.
Measured: Baseline to Week 9
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 13 (Phase 2A)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. the immune parameters will be summarized via percentages of responders and mean/median values, along with corresponding 95% confidence intervals, by treatment arm and measurement time. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For this study, a statistically significant increase in GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline will be considered a response at that time. Significance of the change from baseline will be assessed using the modified distribution-free resampling (DFR) method.
Measured: Baseline to Week 13
Percentage of Participants with a Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 13 (Phase 2A)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals.
Measured: Baseline to Week 13
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2B)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For the dose expansion cohort, the response rate will be estimated with an exact one-sided 95% confidence interval.
Measured: Baseline to Week 5
Percentage of Participants with Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2B)
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For the dose expansion cohort, the response rate will be estimated with an exact one-sided 95% confidence interval.
Measured: Baseline to Week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2019
- Study start10 Nov 2020
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Why it stopped: Protocol is with FDA review, waiting for funding to be released
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Lin, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04111172
- Sponsor's protocol ID
- 19P.785
- Other IDs
- JT 14133
- Status last verified
- Oct 2026
- First submitted
- 20 Sep 2019
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2A/2B, Dose-Finding and Expansion Study of Ad5.F35-hGCC-PADRE Vaccine in Adults With Gastrointestinal Adenocarcinomas at Risk of Relapse Post Definitive Surgery and Standard Therapy
- ClinicalTrials.gov ID
- NCT04111172
- Acronym / sponsor ID
- 19P.785
- Conditions
- Pancreatic Ductal Adenocarcinoma, Colorectal Adenocarcinoma, Gastric Adenocarcinoma, Clinical Stage II Gastric Cancer AJCC v8, Clinical Stage IIA Gastric Cancer AJCC v8, Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8
- Keywords
- circulating tumor DNA, Guanylyl cyclase C, GCC, GUCY2C, ctDNA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Protocol is with FDA review, waiting for funding to be released
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- 10 Nov 2020 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 1 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn whether the Ad5.F35-hGCC-PADRE vaccine is safe and can stimulate an immune response against gastrointestinal (GI) cancers in patients with pancreatic, colorectal, esophageal, gastric, or small bowel adenocarcinomas who have completed surgical resection and standard adjuvant therapy. An additional goal is to evaluate whether the vaccine may help eliminate minimal residual disease (MRD) in ctDNA-positive colon cancer patients.
The main questions it aims to answer are:
Is the Ad5.F35-hGCC-PADRE vaccine safe and tolerable at different dose levels? Does the vaccine induce GCC-specific T-cell immune responses in patients with GI malignancies? In ctDNA-positive colon cancer patients, can the vaccine promote ctDNA clearance as a marker of MRD elimination?
The investigators will compare immune responses across different vaccine dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) to determine the optimal dose.
Participants will:
Receive the Ad5.F35-hGCC-PADRE vaccine by intramuscular injection. Be assigned to one of three dose levels during the dose-finding phase or receive a prespecified dose in the dose-expansion cohort.
Undergo safety assessments, including monitoring for adverse events, injection-site reactions, and laboratory test abnormalities.
Have blood samples collected to evaluate GCC-specific T-cell immune responses. For ctDNA-positive colon cancer patients, undergo ctDNA testing to assess clearance of minimal residual disease.
Detailed description
This is an open-label, dose-finding, single-center, study of Ad5.F35-hGCC-PADRE vaccine delivered intramuscularly in subjects with colorectal, pancreatic, gastric, esophageal, or small bowel cancers who are at high risk of relapse without evidence of disease post definitive surgery and standard therapy.
Study treatment will start after surgery and standard therapy. Subjects who meet the eligibility criteria can participate in this study at least four and no more than 24 weeks ± one week post-completion of standard treatment, after they have recovered from the side effects from previous therapies.
Eligible subjects will be sequentially randomized into three treatment arms of 10¹¹, 10¹², and 5 × 10¹² virus particles Ad5.F35-hGCC-PADRE administered by IM injection once every four weeks (± one week) for a total of three administrations. An initial safety lead-in group of 9 subjects (3 in each group) will be randomized sequentially and further enrollment will be paused until they have completed 4 weeks of follow-up to ensure no dose-limiting toxicities (DLT). Moreover, the enrollment of the first 3 subjects will be staggered by an interval of 3 weeks to monitor for acute and subacute toxicities.
Following the completion of assessment of the initial safety lead-in group, a meeting will be held with the PI and the TJU Medical Monitor to review the safety information. If no excessive rates of DLT are observed, enrollment will continue in each dosing arm with continuous monitoring of adverse events. A total of 27 subjects are planned to be randomized to each treatment arm. If it is determined safe to continue enrollment in each dosing arm, a formal letter from the Medical Monitor will be issued.
After 15 patients in each cohort have completed treatment, a futility analysis will be conducted, and information will be informally reviewed with the Medical Monitor.
In the expansion cohort, subjects with colon cancer who meet eligibility criteria will be enrolled after completing surgery and standard of care adjuvant chemotherapy. There is no limit to the amount of time since completing adjuvant therapies to enroll on this cohort. Subjects who are ctDNA+ by CLIA-certified standard of care assay and fulfil other eligibility criteria can enroll at any point post adjuvant therapies. Subjects will receive single IM vaccination with Ad5.F35-hGCC-PADRE at 5 × 10¹² vp. This dose is selected based upon preliminary efficacy data from first part of this study. Patients will be monitored for adverse events over the course of four weeks. Labs will be collected for immunomonitoring and ctDNA will be collected immediately prior to vaccination, at 4 weeks, 12 weeks and up to 52 weeks post-vaccination. Standard of care ctDNA assessments performed post-vaccination will be collected. Optional research blood samples will be collected for patients who opt in and will be collected every 3 months for up to 24 months or until disease recurrence or death whichever comes first.
PRIMARY OBJECTIVES:
- Evaluate the safety and tolerability of sequential Ad5.F35-hGCC-PADRE vaccine administration, delivered intramuscularly (IM) at three dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) four weeks apart in subjects with high-risk colorectal, pancreatic, gastric, esophageal, or small bowel adenocarcinomas with no evidence of disease after surgery and standard therapy.
- For Cohort 2B, evaluate the safety and tolerability of single Ad5.F35-hGCC-PADRE vaccine at 5 × 10¹² vp dose level in MRD+ colon cancer patients with no evidence of radiographic disease
- Evaluate the cellular (T-cell) responses to Ad5.F35-hGCCPADRE at three different dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) administered intramuscularly (IM) as three sequential doses four weeks apart in subjects with high-risk colorectal, pancreatic, gastric, esophageal, or small bowel adenocarcinomas with no evidence of disease after surgery and standard therapy.
- For cohort 2B, evaluate the cellular (T-cell) responses to Ad5.F35-hGCC-PADRE vaccine at 5 × 10¹² vp dose administered IM as one dose in subjects with MRD+ colon cancer with no evidence of radiographic disease after surgery and standard therapy.
EXPLORATORY OBJECTIVES:
- Evaluate the humoral (antibody) responses to Ad5.F35-hGCC-PADRE at three different dose levels (10¹¹, 10¹², and 5 × 10¹² virus particles) administered IM as three sequential doses four weeks apart in subjects with high-risk colorectal, pancreatic, gastric, esophageal, or small bowel adenocarcinomas with no evidence of disease after surgery and standard therapy
- Evaluate the association of neutralizing antibodies to Ad5 with immunologic response
- Evaluate the correlation of the immune response to the GCC protein expression in tumors to assess immune tolerance
- Evaluate disease-free survival (DFS)
- Evaluate overall survival (OS), where feasible
- Evaluate the circulatory tumor DNA (ctDNA) status and correlation with clinical recurrence, where feasible
- Evaluate the ctDNA dynamics after single dose of 5 × 10¹² vp Ad5.F35-hGCC-PADRE vaccine in an expansion cohort of ctDNA+ colon cancer patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A (low dose) | Experimental | Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADREPatients receive low dose Ad5.F35-hGCC-PADRE vaccine IM on day 1 of weeks 1, 5, and 9 in the absence of disease progression or unacceptable toxicity. |
| Arm B (medium dose) | Experimental | Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADREPatients receive medium dose Ad5.F35-hGCC-PADRE vaccine IM on day 1 of weeks 1, 5, and 9 in the absence of disease progression or unacceptable toxicity. |
| Arm C (high dose) | Experimental | Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADREPatients receive high dose Ad5.F35-hGCC-PADRE vaccine IM on day 1 of weeks 1, 5, and 9 in the absence of disease progression or unacceptable toxicity. |
| Cohort 2B/Expansion Cohort--ctDNA+ Colon Cancer | Experimental | Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADREA group of 20 colon cancer patients who are ctDNA+ by CLIA-certified standard of care assays will receive a single administration of Ad5.F35-hGCC-PADRE vaccine intramuscularly at prespecified dose of 5 × 10¹² vp. Subjects will be followed for the duration of the study until all subjects have reached at least 24 months of follow-up or death. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study:
- 1. Males or females aged ≥ 18 years 2. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 3. Subjects with tumors specified below, who are at high risk of relapse, have been treated with curative intent, and have no evidence of disease (NED) following front-line therapy with surgery, radiation therapy, and/or chemotherapy. NED includes, where applicable, surgical (macroscopic tumor margin, at the time of surgery), and radiological evidence of disease. Residual lesions identified by microscopic/frozen margins and biochemical markers are permitted. Therapy must have been completed no fewer than four weeks, and no later than 25 weeks, before the first dose of Ad5.F35-hGCC-PADRE. For expansion cohort (2B), colon cancer patients may be enrolled four weeks after completion of standard adjuvant therapies, however there is no upper limit to enrollment as long as patients fulfil other eligibility requirements are ctDNA+.
- Pancreatic ductal adenocarcinoma i. Stage I, II, III
- Neuroendocrine tumors of the pancreas are not permitted b. Colorectal adenocarcinoma i. Stage III; Stage IV following metastasectomy ii. High risk stage II colon cancer defined as (any of):
- Gastrointestinal stromal tumors of the stomach are not permitted d. Esophageal adenocarcinoma i. Stage IIB, III
Key exclusion criteria (21 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adenovirus 5/F35-Human Guanylyl Cyclase C-PADREAlso: Ad5.F35-hGCC-PADRE, Ad5/F35-hGCC-PADRE, Adenovirus 5/F35-HGCC-PADREGiven as intramuscular injection | Biological | Arm A (low dose), Arm B (medium dose), Arm C (high dose), Cohort 2B/Expansion Cohort--ctDNA+ Colon Cancer |
Primary outcome
Percentage of Participants with Treatment-Emergent Adverse Events (Phase 2A)
Time frame: Up to 13 weeks
The percentage of subjects with AEs and DLTs will be summarized along with corresponding 95% confidence intervals for each treatment arm and overall. Within each treatment arm, with 24 patients per cohort, if no AEs are observed, the exact 95% confidence interval extends from 0 to 0.14. If one AE is observed, the exact 95% CI extends from 0.001 to 0.21.
Percentage of Participants with Treatment-Emergent Adverse Events (Phase 2B)
Time frame: Up to 5 weeks
The percentage of subjects with AEs and DLTs will be summarized along with corresponding 95% confidence intervals for each treatment arm and overall. Within each treatment arm, with 24 patients per cohort, if no AEs are observed, the exact 95% confidence interval extends from 0 to 0.14. If one AE is observed, the exact 95% CI extends from 0.001 to 0.21.
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2A)
Time frame: Baseline to Week 5
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. the immune parameters will be summarized via percentages of responders and mean/median values, along with corresponding 95% confidence intervals, by treatment arm and measurement time. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For this study, a statistically significant increase in GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline will be considered a response at that time. Significance of the change from baseline will be assessed using the modified distribution-free resampling (DFR) method.
Percentage of Participants with a Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2A)
Time frame: Baseline to Week 5
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals.
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 9 (Phase 2A)
Time frame: Baseline to Week 9
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. the immune parameters will be summarized via percentages of responders and mean/median values, along with corresponding 95% confidence intervals, by treatment arm and measurement time. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For this study, a statistically significant increase in GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline will be considered a response at that time. Significance of the change from baseline will be assessed using the modified distribution-free resampling (DFR) method.
Percentage of Participants with a Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 9 (Phase 2A)
Time frame: Baseline to Week 9
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals.
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 13 (Phase 2A)
Time frame: Baseline to Week 13
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. the immune parameters will be summarized via percentages of responders and mean/median values, along with corresponding 95% confidence intervals, by treatment arm and measurement time. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For this study, a statistically significant increase in GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline will be considered a response at that time. Significance of the change from baseline will be assessed using the modified distribution-free resampling (DFR) method.
Percentage of Participants with a Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 13 (Phase 2A)
Time frame: Baseline to Week 13
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5, 9, or 13 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals.
Magnitude of Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2B)
Time frame: Baseline to Week 5
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For the dose expansion cohort, the response rate will be estimated with an exact one-sided 95% confidence interval.
Percentage of Participants with Guanylyl Cyclase C (GCC)-Specific T-Cell Response at Week 5 (Phase 2B)
Time frame: Baseline to Week 5
Will be measured by enzyme-linked immunosorbent spot (ELISpot) assay. Percentage of participants achieving a positive GCC-specific T-cell response at Weeks 5 compared with baseline. Antibody and T-cell data will be summarized by positive response rates (each subject recorded as yes/no) and exact 2-sided 95% confidence intervals. For the dose expansion cohort, the response rate will be estimated with an exact one-sided 95% confidence interval.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Pancreatic Ductal Adenocarcinoma
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 1
Modified FOLFIRINOX and Pentamidine in Advanced and Metastatic Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
RecruitingPhase 3
Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Lin, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE in people with Pancreatic Ductal Adenocarcinoma and Colorectal Adenocarcinoma, run by Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants with Treatment-Emergent Adverse Events (Phase 2A) (time frame: Up to 13 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.