A Vaccine (Ad5.F35-hGCC-PADRE) for the Treatment of Gastrointestinal Adenocarcinoma

September 9, 2026 updated by: Thomas Jefferson University

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

This is an open-label, dose-finding, Phase 2A/2B study of Ad5.F35-hGCC-PADRE as a vaccine for gastrointestinal (GI) malignancies (pancreatic, colorectal, esophageal, gastric, and small bowel adenocarcinomas) who have received surgical resection and standard adjuvant therapy. In Phase 2A, patients will be given multiple administrations of Ad5.F35-hGCC-PADRE intramuscularly at 1 of 3 dose levels. Treatment-related toxicity and development of immune responses to GCC will be evaluated at Weeks 5, 9, and 13 after the initial vaccination (Week 1). Primary safety endpoints will examine adverse events (AEs), injection-site reactions and clinically-significant changes in safety laboratory tests. Primary efficacy endpoints include the development of GCC-specific T-cell responses at different dose levels (1011, 1012, and 5x1012 virus particles or vp). In Phase 2B Dose Expansion cohort, 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 1012 vp. Phase 2b is NOT randomized. Primary safety endpoints will examine AEs, injection-site reactions and clinically significant changes in safety laboratory tests. The primary efficacy endpoints include GCC-specific T-cell responses at 1012 vp in ctDNA+ patients. Additional exploratory endpoint will determine elimination of minimal residual disease (MRD) by ctDNA clearance.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

  1. Evaluate the safety and tolerability of sequential Ad5.F35-hGCC-PADRE vaccine administration, delivered intramuscularly (IM) at three dose levels (1011, 1012, and 5x1012 vp) 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.
  2. For Cohort 2B, evaluate the safety and tolerability of single Ad5.F35-hGCC-PADRE vaccine at 1012 dose level in MRD+ colon cancer patients with no evidence of radiographic disease
  3. Evaluate the cellular (T-cell) responses to Ad5.F35-hGCCPADRE at three different dose levels (1011, 1012, and 5x1012 vp) 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.
  4. For cohort 2B, evaluate the cellular (T-cell) responses to Ad5.F35-hGCC-PADRE vaccine at 1012 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 5x1012 vp) 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 1012 Ad5.F35-hGCC-PADRE vaccine in an expansion cohort of ctDNA+ colon cancer patients

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • 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 tumor-specific criteria, please refer to the information below:

    * Pancreatic ductal adenocarcinoma

    ** Stage I, II, III

    • Neuroendocrine tumors of the pancreas are not permitted

      * Colorectal adenocarcinoma

      • Stage III; stage IV following metastasectomy

        * Gastric adenocarcinoma

      • Stage IIA, IIB, III

    • Gastrointestinal stromal tumors of the stomach are not permitted

      * Esophageal adenocarcinoma

      ** Stage IIB, III

    • Esophageal squamous cell carcinomas are not permitted
  • Have an anticipated life expectancy of greater than 12 weeks
  • Absolute neutrophil count (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 Common Terminology Criteria for Adverse Events (CTCAE), National Cancer Institute (NCI) version 5 issued by the United States (US) Department of Health and Human Services
  • 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
  • Be willing to comply with all the study procedures
  • All subjects must be able to comprehend and sign a written informed consent document

Exclusion Criteria:

  • Have a known history or evidence of residual disease after definitive surgery
  • Have a known metastasis in the brain or central nervous system
  • Prior receipt of immunotherapy or experimental medications after completion of standard adjuvant therapy
  • 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)
  • 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 human immunodeficiency virus (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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (low dose)
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.
Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE
Given as intramuscular injection
Other Names:
  • Ad5.F35-hGCC-PADRE
  • Ad5/F35-hGCC-PADRE
  • Adenovirus 5/F35-HGCC-PADRE
Experimental: Arm B (medium dose)
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.
Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE
Given as intramuscular injection
Other Names:
  • Ad5.F35-hGCC-PADRE
  • Ad5/F35-hGCC-PADRE
  • Adenovirus 5/F35-HGCC-PADRE
Experimental: Arm C (high dose)
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.
Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE
Given as intramuscular injection
Other Names:
  • Ad5.F35-hGCC-PADRE
  • Ad5/F35-hGCC-PADRE
  • Adenovirus 5/F35-HGCC-PADRE
Experimental: Cohort 2B/Expansion Cohort--ctDNA+ Colon Cancer
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 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.
Biological: Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE
Given as intramuscular injection
Other Names:
  • Ad5.F35-hGCC-PADRE
  • Ad5/F35-hGCC-PADRE
  • Adenovirus 5/F35-HGCC-PADRE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events (AEs)
Time Frame: 13 weeks
AEs classified by System Organ Class, preferred term, severity, and relationship to study treatment, and graded in accordance with the document entitled "Common Terminology Criteria for Adverse Events" (CTCAE), National Cancer Institute version 5 issued by the United States Department of Health and Human Services. Injection-site reactions including, but not necessarily limited to, local skin erythema, induration, pain and tenderness at administration site. Clinically-significant changes in safety laboratory tests. The percentage of subjects with AEs and DLTs will be summarized along with corresponding 95% confidence intervals for each treatment arm and overall.
13 weeks
Antigen-specific T-cell response to guanylyl cyclase C (GCC)
Time Frame: 13 weeks
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. Will estimate response rates across disease types.
13 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas Jefferson University

Investigators

  • Principal Investigator: Babar Bashir, MD, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 10, 2020

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

September 20, 2019

First Submitted That Met QC Criteria

September 27, 2019

First Posted (Actual)

October 1, 2019

Study Record Updates

Last Update Posted (Actual)

September 14, 2026

Last Update Submitted That Met QC Criteria

September 9, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19P.785
  • JT 14133 (Other Identifier: JeffTrial Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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