Clinical Trials /

Trial of PalloV-CC in Colon Cancer

NCT03827967

Description:

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.

Related Conditions:
  • Colon Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: PV-CC-01
  • NCT ID: NCT03827967

Conditions

  • Colon Cancer

Interventions

DrugSynonymsArms
PalloV-CC1x10^8 particles of PalloV-CC

Purpose

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.
      Subjects 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
      subjects about being in the trial and will introduce the trial to the prospective volunteer
      subject. If the subject 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 108 particles of PalloV-CC

        2. 2 x 108 particles of PalloV-CC

        3. 4 x 108 particles of PalloV-CC

        4. 8 x 108 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).
      Study subjects may opt out of the collection of study blood (150 mL total over three blood
      draws).
    

Trial Arms

NameTypeDescriptionInterventions
1x10^8 particles of PalloV-CCExperimentalIntradermal injection of PalloV-CC weekly x 4 weekly
  • PalloV-CC
2x10^8 particles of PalloV-CCExperimentalIntradermal injection of PalloV-CC weekly x 4 weekly
  • PalloV-CC
4x10^8 particles of PalloV-CCExperimentalIntradermal injection of PalloV-CC weekly x 4 weekly
  • PalloV-CC
8x10^8 particles of PalloV-CCExperimentalIntradermal injection of PalloV-CC weekly x 4 weekly
  • PalloV-CC

Eligibility Criteria

        Inclusion Criteria:

          1. Stage I-IV (resectable) colon cancer subjects 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Primary Safety Endpoint-Overall number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame:1 year for all 4 cohorts to enroll and undergo treatment.
Safety Issue:
Description:To determine the overall safety and toxicity of the PalloV CC vaccine by analyzing number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

Secondary Outcome Measures

Measure:Secondary Endpoint-Effect Tumor Microenvironment measured via Immunoscore
Time Frame:1 year for all 4 cohorts to enroll and undergo treatment.
Safety Issue:
Description:To determine the effect of vaccination on the tumor microenvironment in colon cancer by comparing the Immunoscore (scale range: low, intermediate, high) between matched endoscopic biopsies (pre-vaccination) and resected final specimens (post-vaccination).
Measure:Secondary Endpoint-Immunologic comparison of evaluations of tumor microenvironment
Time Frame:1 year for all 4 cohorts to enroll and undergo treatment.
Safety Issue:
Description:To determine the concordance of Immunoscore (scale range: low, intermediate, high) with other emerging analytical tools such as gene expression data analysis (CIBERSORT) and T-cell receptor sequencing (Immunoseq).
Measure:Secondary Endpoint-PD-L1 expression comparison within the Tumor Microenvironment
Time Frame:1 year for all 4 cohorts to enroll and undergo treatment.
Safety Issue:
Description:Identify PD-L1 expression on tumor cells and compare the pretreatment endoscopic biopsies, post-treatment surgical specimens, and historical controls level of PD-L1 expression.
Measure:Secondary Endpoint-CD4+ and regulatory T cells expression comparison within the Tumor Microenvironment
Time Frame:1 year for all 4 cohorts to enroll and undergo treatment.
Safety Issue:
Description:Identify CD4+ and regulator T cell infiltration into the tumor microenvironment and compare CD4+ and regulatory T Cell quantity between the pretreatment endoscopic biopsies, post-treatment surgical specimens, and the historical controls.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:George E. Peoples

Last Updated

August 12, 2019