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Phase 2A Study of Ad5.F35-hGCC-PADRE in Gastrointestinal Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04111172
Recruitment Status : Not yet recruiting
First Posted : October 1, 2019
Last Update Posted : May 28, 2020
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University

Brief Summary:

This is an open-label, dose-finding, single-center, study of Ad5.F35-hGCC-PADRE vaccine delivered intramuscularly in subjects with colorectal, pancreatic, gastric, or esophageal cancers who are at high risk of relapse without evidence of disease post definitive 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 simultaneously randomized into three treatment arms of 10^11, 10^12, or 5x10^12 vp Ad5.F35-hGCC-PADRE administered by IM injection once every four weeks (± one week) for a total of three administrations. An initial safety group of 9 subjects (3 in each group) will be randomized and further enrollment will be paused until they have completed 4 weeks of follow-up to ensure no dose-limiting toxicities.


Condition or disease Intervention/treatment Phase
Pancreatic Ductal Adenocarcinoma Colorectal Adenocarcinoma Gastric Adenocarcinoma Esophageal Adenocarcinoma Biological: Ad5.F35-hGCC-PADRE Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Evaluate the safety and tolerability of sequential Ad5.F35-hGCC-PADRE, delivered intramuscularly three times at three dose levels in subjects with high-risk colorectal, pancreatic, gastric, or esophageal adenocarcinomas with no evidence of disease (NED) after surgery and standard therapy

II. Evaluate the cellular (T-cell) responses to Ad5.F35-hGCC-PADRE at three different dose levels (10^11, 10^12, and 5x10^12 vp) administered intramuscularly three times, four weeks apart in subjects with high-risk colorectal, pancreatic, gastric, or esophageal cancer with NED after surgery and standard therapy.

EXPLORATORY OBJECTIVES:

I. Evaluate the humoral immunologic response to GCC, defined as an incremental or sustained antibody (pan-Ig) response, measured at Weeks 5, 9, and 13 following the first vaccination (Week 1).

II. Evaluate the relationship between immunological responses to GCC and 1) neutralizing antibodies to Ad5 and Ad5.F35 and 2) GCC protein expression in tumors to assess immune tolerance.

III. Evaluate DFS and OS, where feasible.

OUTLINE: Patients are randomized to 1 of 3 arms. A safety cohort of 3 patients per arm (9 total) will be enrolled first. If determined safe to continue, additional patients will be enrolled.

ARM I: After completion of definitive surgery and standard therapy, Ad5.F35-hGCC-PADRE at 10^11vp Day 1 of Weeks 1, 5, and 9

ARM II: After completion of definitive surgery and standard therapy, Ad5.F35-hGCC-PADRE at 10^12vp Day 1 of Weeks 1, 5, and 9

ARM III: After completion of definitive surgery and standard therapy, Ad5.F35-hGCC-PADRE at 5x10^12vp Day 1 of Weeks 1, 5, and 9

After completion of study treatment, patients are followed periodically for 24 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2A, Dose-Finding Study of Ad5.F35-hGCC-PADRE Vaccine in Adults With Gastrointestinal Adenocarcinomas at Risk of Relapse Post Definitive Surgery and Standard Therapy
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2024

Arm Intervention/treatment
Experimental: Arm A
Receive Ad5.F35-hGCC-PADRE vaccine at 10^11vp on Day 1 of Weeks 1, 5, and 9
Biological: Ad5.F35-hGCC-PADRE
Given as intramuscular injection

Experimental: Arm B
Receive Ad5.F35-hGCC-PADRE vaccine at 10^12vp on Day 1 of Weeks 1, 5, and 9
Biological: Ad5.F35-hGCC-PADRE
Given as intramuscular injection

Experimental: Arm C
Receive Ad5.F35-hGCC-PADRE vaccine at 5x10^12vp on Day 1 of Weeks 1, 5, and 9
Biological: Ad5.F35-hGCC-PADRE
Given as intramuscular injection




Primary Outcome Measures :
  1. Number of Patients with Adverse Events related to Ad5.F35-hGCC-PADRE vaccine [ Time Frame: From baseline to Week 13 ]
    Based on clinically significant changes in safety laboratory tests, injection site reactions, and clinical adverse event monitoring. These events will be looked at collectively to determine the number of adverse events that were recording from baseline through Week 13.

  2. Evaluation of cellular (T-cell) responses to Ad5.F35-hGCC-PADRE vaccine [ Time Frame: From baseline to Week 13 ]
    antigen-specific T-cell response to GCC measured by ELISpot assay



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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
  4. For tumor-specific criteria, please refer to the information below:

    a. 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 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
  5. Have an anticipated life expectancy of greater than 12 weeks
  6. Have adequate organ function at screening

    1. ANC ≥ 1000 cells/mL
    2. Platelets ≥ 75,000 /mL
    3. Hemoglobin ≥ 9.0 g/dL
    4. Serum creatinine < 2.0 mg/dL
    5. 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. For subjects who are at advanced stages of disease (Stage III and above, in general), by the investigator's discretion and after consultation with PI, test results may not be worse than Grade 2 levels of abnormalities defined by CTCAE v5.
  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

Exclusion Criteria:

  1. Have a known history or evidence of residual disease after definitive surgery
  2. Have a known metastasis in the brain or central nervous system
  3. Prior receipt of immunotherapy or experimental medications after completion of standard adjuvant therapy
  4. Have a history of splenectomy
  5. Have a history of distal pancreatectomy
  6. Concurrent use of systemic steroids or immunosuppressive drugs (use of topical or inhaled steroids will be allowed, see Section 5.7)
  7. Have any immunodeficiency disease or immunocompromised state (e.g., use of immunosuppressive agents, chemotherapy or radiation therapy within four weeks of study treatment)
  8. Have active autoimmune disease or history of autoimmune disease or a transplant recipient requiring systemic steroids or other immunosuppressive treatment
  9. 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)
  10. 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
  11. Have a history of inflammatory bowel disease
  12. Have a history of serious reaction to adenovirus
  13. 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)
  14. Have insufficient peripheral venous access to permit completion of the study phlebotomy regimen
  15. 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
  16. 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
  17. Be a woman who is pregnant or breastfeeding
  18. Have an unhealed surgical wound
  19. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04111172


Contacts
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Contact: Babar Bashir, MD 215-955-8874 babar.bashir@jefferson.edu

Locations
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United States, Pennsylvania
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Contact: Babar Bashir, MD    215-955-8874    babar.bashir@jefferson.edu   
Sponsors and Collaborators
Thomas Jefferson University
Investigators
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Principal Investigator: Babar Bashir, MD Sidney Kimmel Cancer Center at Thomas Jefferson University
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Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT04111172    
Other Study ID Numbers: 14133
First Posted: October 1, 2019    Key Record Dates
Last Update Posted: May 28, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms