A Phase I, Single-Center, Dose Escalation Trial of Heterologous Prime-Boost Vaccination With Ad5.F35-hGUCY2C-PADRE and Lm-GUCY2C Vaccines in Adults With Advanced Colorectal and Small Bowel Adenocarcinomas
Thomas Jefferson University
Summary
This is an open-label, non-randomized, single-center, dose-escalation Phase 1 trial using a heterologous prime-boost strategy of vaccination with Ad5.F35-hGUCY2C-PADRE and recombinant Listeria monocytogenes (Lm-GUCY2C) vaccines in patients with advanced solid tumors including colorectal cancer, and small bowel adenocarcarcinomas who have progressed on available standard therapies. The study treatment will begin with Ad5.F35-hGUCY2C-PADRE vaccine administered intramuscularly (IM) once at the recommended Phase 2 dose (RPTD) dose, followed four weeks later by two administrations of Lm-GUCY2C intravenously (IV) at one of three escalating dose levels, four weeks apart. Treatment-related toxicity and development of immune responses will be evaluated every four weeks through week 8 after initial Lm-GUCY2C vaccination. Primary endpoints will include maximum tolerated dose (MTD) and safety and tolerability as measured by treatment emergent adverse events (TEAEs) and clinically significant changes in safety laboratory tests in the dose limiting toxicity (DLT) evaluation period defined as 4 weeks after the initial Lm-GUCY2C vaccination.
Description
This phase 1 study is an open-label study of heterologous prime-boost vaccination with Ad5.F35-hGUCY2C-PADRE and recombinant listeria monocytogenes (Lm-GUCY2C) vaccines in patients with advanced solid tumors including colorectal cancer and small bowel adenocarcinomas who have progressed on available standard therapies.. Subjects will receive Ad5.F35-hGUCY2C-PADRE intramuscularly (IM) followed by two administrations of the Lm-GUCY2C vaccine intravenously (IV) as described and will be followed primarily to evaluate safety endpoints for the duration of the study (through eight weeks after the fir…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study: 1. Males or females aged ≥ 18 years 2. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 3. Histologically or cytologically diagnosed, locally advanced or metastatic adenocarcinomas of colorectum or small bowel that have progressed after standard of care therapy or for which no standard therapy exists. Patients for whom standard therapies are intolerable or considered clinically inappropriate by the Investigator are eligible.…
Interventions
- BiologicalAd5.F35-hGUCY2C-PADRE vaccine
Ad5.F35-hGUCY2C-PADRE vaccine administered as a single intramuscular injection at a dose of 5 × 10¹² viral particles as the priming vaccination in a heterologous prime-boost vaccination regimen.
- BiologicalLm-GUCY2C vaccine
Lm-GUCY2C vaccine administered as an intravenous infusion at dose levels 1 x 10⁸, 3 x 10⁸, 1 x 10⁹, and 3 x 10⁹ colony-forming units (CFU) as booster vaccinations given twice approximately four weeks apart following Ad5.F35-hGUCY2C-PADRE priming.
- Diagnostic TestCT Scan
Spiral CT of thorax, abdomen, and pelvis (and other imaging studies as clinically indicated) for disease assessment at Screening and EOT. If a subject cannot have a CT scan (e.g., allergy to contrast dye), MRI results are acceptable.
Location
- Sidney Kimmel Cancer Center at Thomas Jefferson UniversityPhiladelphia, Pennsylvania