Trial of PalloV-CC in Colon Cancer

NCT ID: NCT03827967

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-20
• Study Completion Date: 2023-05-20

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).

Conditions

Colon Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1x10^8 particles of PalloV-CC

Intradermal injection of PalloV-CC weekly x 4 weekly

Group Type: EXPERIMENTAL

PalloV-CC

Intervention Type: BIOLOGICAL

The PalloV-CC vaccine uses yeast cell wall particles (YCWP) to serve as an efficient vaccine delivery system as they can contain a broad range of antigenic material, they are rapidly phagocytized by antigen presenting cells, and they are inherently immunogenic. The PalloV-CC vaccine utilizes silicate-capped YCWP to deliver allogenic colon cancer tumor lysate. The vaccine will be given to subjects with resectable colon cancers neoadjuvantly shortly before surgery in order to study the effect of the vaccine on the tumor microenvironment using a well-validated immune scoring system for colon cancer and other immunologic tests.

2x10^8 particles of PalloV-CC

Intradermal injection of PalloV-CC weekly x 4 weekly

Group Type: EXPERIMENTAL

PalloV-CC

Intervention Type: BIOLOGICAL

The PalloV-CC vaccine uses yeast cell wall particles (YCWP) to serve as an efficient vaccine delivery system as they can contain a broad range of antigenic material, they are rapidly phagocytized by antigen presenting cells, and they are inherently immunogenic. The PalloV-CC vaccine utilizes silicate-capped YCWP to deliver allogenic colon cancer tumor lysate. The vaccine will be given to subjects with resectable colon cancers neoadjuvantly shortly before surgery in order to study the effect of the vaccine on the tumor microenvironment using a well-validated immune scoring system for colon cancer and other immunologic tests.

4x10^8 particles of PalloV-CC

Intradermal injection of PalloV-CC weekly x 4 weekly

Group Type: EXPERIMENTAL

PalloV-CC

Intervention Type: BIOLOGICAL

The PalloV-CC vaccine uses yeast cell wall particles (YCWP) to serve as an efficient vaccine delivery system as they can contain a broad range of antigenic material, they are rapidly phagocytized by antigen presenting cells, and they are inherently immunogenic. The PalloV-CC vaccine utilizes silicate-capped YCWP to deliver allogenic colon cancer tumor lysate. The vaccine will be given to subjects with resectable colon cancers neoadjuvantly shortly before surgery in order to study the effect of the vaccine on the tumor microenvironment using a well-validated immune scoring system for colon cancer and other immunologic tests.

8x10^8 particles of PalloV-CC

Intradermal injection of PalloV-CC weekly x 4 weekly

Group Type: EXPERIMENTAL

PalloV-CC

Intervention Type: BIOLOGICAL

The PalloV-CC vaccine uses yeast cell wall particles (YCWP) to serve as an efficient vaccine delivery system as they can contain a broad range of antigenic material, they are rapidly phagocytized by antigen presenting cells, and they are inherently immunogenic. The PalloV-CC vaccine utilizes silicate-capped YCWP to deliver allogenic colon cancer tumor lysate. The vaccine will be given to subjects with resectable colon cancers neoadjuvantly shortly before surgery in order to study the effect of the vaccine on the tumor microenvironment using a well-validated immune scoring system for colon cancer and other immunologic tests.

Interventions

PalloV-CC

The PalloV-CC vaccine uses yeast cell wall particles (YCWP) to serve as an efficient vaccine delivery system as they can contain a broad range of antigenic material, they are rapidly phagocytized by antigen presenting cells, and they are inherently immunogenic. The PalloV-CC vaccine utilizes silicate-capped YCWP to deliver allogenic colon cancer tumor lysate. The vaccine will be given to subjects with resectable colon cancers neoadjuvantly shortly before surgery in order to study the effect of the vaccine on the tumor microenvironment using a well-validated immune scoring system for colon cancer and other immunologic tests.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

George E. Peoples

INDUSTRY

Sponsor Role: lead

Responsible Party

George E. Peoples

CEO, Cancer Insight, LLC

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

George Peoples, MD, FACS

Role: PRINCIPAL_INVESTIGATOR

LumaBridge

Locations

Clinical Associates of Research Therapeutics of America

San Antonio, Texas, United States

Countries

United States

Other Identifiers

PV-CC-01

Identifier Type: -

Identifier Source: org_study_id