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.
Recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Adenovirus 5/F35-Human Guanylyl Cyclase C-PADRE | Ad5.F35-hGCC-PADRE, Ad5/F35-hGCC-PADRE, Adenovirus 5/F35-HGCC-PADRE | Arm A (low dose) |
PRIMARY OBJECTIVES:
I. Evaluate the safety and tolerability of sequential adenovirus 5/F35-human guanylyl cyclase
C-PADRE (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 5 x 10^12 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 guanylyl cyclase C (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 disease free survival (DFS) and overall survival (OS), where feasible.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A: Patients receive low dose Ad5.F35-hGCC-PADRE vaccine intramuscularly (IM) on day 1 of
weeks 1, 5, and 9 in the absence of disease progression or unacceptable toxicity.
ARM B: 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.
ARM C: 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.
After completion of study treatment, patients are followed up at 28 days, and then every 3
months for at least 24 months.
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
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)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Incidence of adverse events (AEs) |
| Time Frame: | 13 weeks |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Thomas Jefferson University |
June 7, 2021
