Clinical trial NCT03827967: Trial of PalloV-CC in Colon Cancer
Official title: A Phase Ib Trial of Neoadjuvant PalloV-CC (Particle-delivered, Allogeneic Tumor Cell Lysate Vaccine for Colon Cancer) in Colon Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colon Cancer
Lead sponsor: Cancer Insight, LLC
Sponsor class: INDUSTRY
First posted: 2019-02-04
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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, each patient treatment period is 4 weeks. Patients will conclude treatment with colectomy.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Primary Safety Endpoint-Overall number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
measure: Primary Safety Endpoint-Per Dosing Cohort number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
measure: Primary Immunologic Endpoint-Overall Immunoscore of the tumor microenvironment
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
measure: Primary Immunologic Endpoint-Per Dosing Cohort Immunoscore of the tumor microenvironment
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
Secondary outcomes:
measure: Secondary Endpoint-Effect Tumor Microenvironment measured via Immunoscore
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
measure: Secondary Endpoint-Immunologic comparison of evaluations of tumor microenvironment
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
measure: Secondary Endpoint-PD-L1 expression comparison within the Tumor Microenvironment
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
measure: Secondary Endpoint-CD4+ and regulatory T cells expression comparison within the Tumor Microenvironment
timeFrame: 1 year for all 4 cohorts to enroll and undergo treatment.
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Clinical Associates of Research Therapeutics of America
state: Texas
Study officials:
affiliation: LumaBridge
name: George Peoples, MD, FACS
role: PRINCIPAL_INVESTIGATOR
References: