Vaccine for Gastrointestinal Cancer

Overseen By Babar Bashir

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 9 weeks

81 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase IIA trial investigates the side effects of Ad5.F35-hGCC-PADRE vaccine and to see how well it works in treating patients with gastrointestinal adenocarcinoma. Ad5.F35-hGCC-PADRE vaccine may help to train the patient's own immune system to identify and kill tumor cells and prevent it from coming back.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use systemic steroids or immunosuppressive drugs during the trial.

What data supports the effectiveness of the treatment Ad5.F35-hGCC-PADRE for gastrointestinal cancer?

The Ad5-GUCY2C-PADRE vaccine, which is similar to Ad5.F35-hGCC-PADRE, has shown safety and the ability to trigger immune responses in early-stage colorectal cancer patients, suggesting potential effectiveness in gastrointestinal cancers. ^{1 2 3 4 5}

Is the Ad5.F35-hGCC-PADRE vaccine safe for humans?

The Ad5-GUCY2C-PADRE vaccine, similar to Ad5.F35-hGCC-PADRE, was tested in a phase I study for colorectal cancer and was found to be safe, with no long-term adverse effects reported. ^{1 2 5 6 7}

What makes the treatment Ad5.F35-hGCC-PADRE unique for gastrointestinal cancer?

The treatment Ad5.F35-hGCC-PADRE is unique because it uses a viral vector to deliver a cancer vaccine, potentially activating the immune system to target cancer cells specifically. This approach is different from traditional treatments as it aims to harness the body's immune response to fight cancer, which may offer a novel way to treat gastrointestinal cancers that lack well-characterized tumor-specific antigens. ^{4 5 8 9 10}

Research Team

Babar Bashir, MD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Eligibility Criteria

This trial is for adults with gastrointestinal adenocarcinoma who've had treatment aiming to cure and currently show no signs of the disease. They must be in good physical condition, not have severe kidney issues, use effective contraception if childbearing potential, and not have other serious health problems or a history of certain diseases.

Inclusion Criteria

You have had certain types of tumors and have been treated with the goal of curing the cancer. After treatment, there is no sign of the disease, with some exceptions for small remaining tumors or certain test results. Treatment must have finished between four and 25 weeks before starting the study.

Have an anticipated life expectancy of greater than 12 weeks

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

Exclusion Criteria

You have received immunotherapy or experimental medications after finishing standard treatment.

You still have signs of the disease even after having surgery to remove it.

You have cancer that has spread to your brain or central nervous system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ad5.F35-hGCC-PADRE vaccine intramuscularly on day 1 of weeks 1, 5, and 9 at varying doses depending on the arm

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

1 visit (in-person)

Long-term Follow-up

Participants are followed up every 3 months for at least 24 months to evaluate disease-free survival and overall survival

24 months

Treatment Details

Interventions

• Ad5.F35-hGCC-PADRE

Trial Overview The trial is testing a vaccine called Ad5.F35-hGCC-PADRE to see how well it works and what side effects it has on patients with gastrointestinal adenocarcinoma. The goal is for the vaccine to teach the immune system to recognize and kill cancer cells.

Participant Groups

Group I: Arm C (high dose) Experimental Treatment 1 Intervention

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.

Group II: Arm B (medium dose) Experimental Treatment 1 Intervention

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.

Group III: Arm A (low dose) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Findings from Research

The OTSGC-A24 cancer vaccine was well tolerated in a phase I/Ib trial with 24 patients suffering from advanced gastric cancer, showing no dose-limiting toxicities and manageable side effects like decreased appetite and injection site reactions.

Significant immune responses were observed, with 90% of patients showing positive cytotoxic T lymphocyte (CTL) responses at 12 weeks, leading to a recommended dosing schedule of 1 mg every 2 weeks for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer. Sundar, R., Rha, SY., Yamaue, H., et al.[2022]

Dendritic cell (DC) vaccines, derived from a patient's own blood, have shown promise in safely initiating specific T cell responses against tumors, with Phase I/II trials indicating minimal side effects.

These vaccines can potentially target a wide range of human cancers, including gastrointestinal cancers, even in cases where specific tumor antigens are not well-defined, making them a versatile option for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell-based cancer immunotherapy: potential for treatment of colorectal cancer? Chen, W., Rains, N., Young, D., et al.[2019]

The dendritic cell vaccine, made from patients' own cells and tumor RNA, was well tolerated in 15 patients with advanced colorectal cancer, with no major adverse effects reported during the treatment.

While no dramatic clinical responses were observed yet, 7 out of 13 patients showed a decrease in carcinoembryonic antigen levels, indicating a potential anticancer effect that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer. Rains, N., Cannan, RJ., Chen, W., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Therapeutic vaccination in patients with gastrointestinal malignancies. A review of immunological and clinical results. [2020]

4. Greece pubmed.ncbi.nlm.nih.gov

Review. Colon cancer vaccines: an update. [2010]

5. Australia pubmed.ncbi.nlm.nih.gov

Dendritic cell-based cancer immunotherapy: potential for treatment of colorectal cancer? [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Human colorectal cancer (CRC) antigen CO17-1A/GA733 encoded by adenovirus inhibits growth of established CRC cells in mice. [2007]

9. United States pubmed.ncbi.nlm.nih.gov

Development of an oral DNA vaccine against MG7-Ag of gastric cancer using attenuated salmonella typhimurium as carrier. [2019]

10. China pubmed.ncbi.nlm.nih.gov

[Development of oral DNA vaccine based on MG(7)-Ag mimotope of gastric cancer]. [2006]