Clinical Trials /

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

NCT04111172

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, 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.

Related Conditions:
  • Colorectal Adenocarcinoma
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2A Study of Ad5.F35-hGCC-PADRE in Gastrointestinal Malignancies
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 14133
  • NCT ID: NCT04111172

Conditions

  • Pancreatic Ductal Adenocarcinoma
  • Colorectal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Esophageal Adenocarcinoma

Interventions

DrugSynonymsArms
Ad5.F35-hGCC-PADREArm A

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalReceive Ad5.F35-hGCC-PADRE vaccine at 10^11vp on Day 1 of Weeks 1, 5, and 9
  • Ad5.F35-hGCC-PADRE
Arm BExperimentalReceive Ad5.F35-hGCC-PADRE vaccine at 10^12vp on Day 1 of Weeks 1, 5, and 9
  • Ad5.F35-hGCC-PADRE
Arm CExperimentalReceive Ad5.F35-hGCC-PADRE vaccine at 5x10^12vp on Day 1 of Weeks 1, 5, and 9
  • Ad5.F35-hGCC-PADRE

Eligibility 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Patients with Adverse Events related to Ad5.F35-hGCC-PADRE vaccine
Time Frame:From baseline to Week 13
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Thomas Jefferson University

Last Updated

May 27, 2020