This study is a phase Ib prospective, open label study evaluating the effect of vaccination
on the immune microenvironment of cancers with results compared to banked tissue from
historical controls. Prospectively vaccinated patients will also serve as their own controls
by comparing the immune microenvironment of the tumor in pre-treatment biopsies to
post-treatment surgical specimens. This is also a dose-escalation study with consecutive
enrollment and advancement of cohorts in an overlapping fashion.
This is a single arm, open label, phase Ib trial of neoadjuvant vaccination in colon cancer.
The primary endpoint is the safety and toxicity of the vaccine. The primary immunologic
endpoint is the impact of vaccination on the tumor microenvironment compared to prospectively
evaluated, tissue banked specimens from historical controls. The tumor microenvironment will
also be compared in matched pre- and post-treatment tissue samples in vaccinated subjects.
Patients with endoscopic biopsy proven colon cancer will be identified by the staff in the
gastroenterology, surgery, and/or the hematology/oncology clinics at the individual study
sites. A research nurse, study coordinator, or study investigator will approach these
patients about being in the trial and will introduce the trial to the prospective volunteer
patient. If the patient is interested and appears eligible, the nurse, study coordinator, or
investigator will arrange an appointment to counsel and consent the patient. Once consent is
obtained, the nurse, study coordinator, or investigator will thoroughly screen the patient
for inclusion and exclusion eligibility criteria.
If volunteers meet all inclusion criteria and none of the exclusion criteria and agree to
participate, they will continue in the study, consented and enrolled for treatment
assignment. Enrollment will start in cohort 1 with enrollment of 6 patients, and follow
sequentially into the remaining cohorts, until all cohorts are completed. After treatment of
all 6 patients in each dose cohort, a comprehensive safety analysis will be performed for
short-term toxicity. If no dose limiting toxicity (DLT, >grade 2, related, or serious adverse
event (SAE)) is found, then the next cohort will be enrolled. If three patients in a given
dose cohort experience a DLT, then that dose will be determined to be the maximal tolerated
dose (MTD), and the next dose cohort will not be initiated. At the completion of dosing of
cohorts (last surgical colectomy performed), a comprehensive safety analysis will be
performed for long-term toxicity. If the MTD is not reached, then a total of 24 patients will
be enrolled.
Treatment cohorts (each n=6, total of n=24):
1. 1 x 10^8 particles of PalloV-CC
2. 2 x 10^8 particles of PalloV-CC
3. 4 x 10^8 particles of PalloV-CC
4. 8 x 10^8 particles of PalloV-CC
PalloV-CC is inoculated weekly via intradermal injection. There will be sequential enrollment
of dose-escalation cohorts (Appendix A), each patient treatment period is 4 weeks (Appendix
B). Patients will conclude treatment with colectomy.
Safety data will be collected on local and systemic toxicities and graded and reported per
the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
A total of 190 mL of blood will be drawn throughout the course of the study over a 3-4 week
period. The patient will have 70mL of blood drawn for the following: a CBC with differential
(10 mL of blood), a CMP (10 mL of blood), and study blood (50 mL of blood). This will be
drawn on two separate occasions: once prior to the first vaccine inoculation, and again after
the completion of the final vaccine inoculation (but prior to surgery). An additional 50 mL
of study blood will be drawn midway through the vaccine series (at the third inoculation).
Inclusion Criteria:
1. Stage I-IV (resectable) colon cancer patients identified prior to their definitive
surgery
2. Diagnosis definitively confirmed by endoscopic biopsy with tumor tissue slides
available for analysis
3. Asymptomatic and capable of waiting 4 weeks prior to definitive surgery
4. ECOG 0-1 performance
5. Not involved in other clinical trials
6. Capable of giving informed consent
Exclusion Criteria:
1. Symptoms of obstruction or GI bleeding that necessitate more urgent surgical
intervention
2. Cancer not definitively confirmed on endoscopic biopsy (i.e., Only high-grade
dysplasia or adenoma identified, even if malignancy is suspected)
3. Known immune deficiency disease or HIV, active HBV, or active HCV
4. Steroids or other immunosuppressants received within 6 weeks of enrollment
5. Any colon cancer directed treatment (chemotherapy or radiation) received or planned
prior to surgical resection
6. A history of any hematologic malignancy or myeloproliferative disease within 5 years
prior to enrollment
7. Leukopenia or neutropenia within two weeks of presentation
8. ECOG >/= 2
9. Pregnancy (serum or urine HCG) or breast feeding
10. Tbili >1.8, Cr >2, Hgb <10, platelet count <50,000, WBC <2,000
