Personalized Vaccine with SOC Chemo Followed by Nivo in Pancreatic Cancer

NCT04627246 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: CHUV-DO-0011-PC_PEP-DC_2017
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Phase Ib clinical trial using Autologous Dendritic Cell Vaccine Loaded with Personalized Peptides (PEP) in order to stimulate/induce both innate and adaptive immunity by activating T-cells and Natural Killer (NK) cells, combined with standard of care (SOC) adjuvant chemotherapy, followed by nivolumab, an antibody against Programmed Cell Death 1 (PD-1), to maintain and boost the vaccine's effect in patients with non-metastatic resectable pancreatic adenocarcinoma

Conditions

Pancreatic Adenocarcinoma

Keywords

Pancreas; vaccine; nivolumab; cancer; adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Number of cases for which vaccine is produced

  Feasibility will be assessed measuring the number of cases, in which vaccine is produced successfully (defined as production and quality control release of at least 5 PEP-DC vaccines for a patient) among the enrolled patients and number of patients who receive at least one dose of vaccine

  3 years after study activation

• Assessment of adverse events

  Collection of adverse events and serious adverse events, treatment limiting toxicities and assessment of immunogenicity

  3 years after study activation

Secondary Outcomes (6)

• Relapse free survival

  8 years

• Overall survival

  8 years

• Gene analysis of immunological response

  8 years

• Cell analysis of immunological response

  8 years

• Evaluation of tumor marker carbohydrate antigene 19-9 (CA19-9) or carcinoembryonic antigen (CEA) kinetics

  8 years

Study Arms (1)

PEP-DC + Nivolumab + SOC

EXPERIMENTAL

PEP-DC: Autologous Dendritic Cell Vaccine Loaded with Personalized Peptides Nivolumab SOC: Standard of Care Chemotherapy

Biological: Autologous Dendritic Cell Vaccine Loaded with Personalized Peptides (PEP-DC vaccine)

Interventions

Autologous Dendritic Cell Vaccine Loaded with Personalized Peptides (PEP-DC vaccine) BIOLOGICAL

SOC: Subgroup1: intravenous mFOLFIRINOX for twelve 14-day cycles. Subgroup2: intravenous gemcitabine twice, on days 1 and 8, and oral capecitabine for 14 days of 21-day cycles, for eight cycles. PEP-DC vaccine: At least 5 subcutaneous vaccinations starting on cycle 8 (subgroup1) or cycle 5 (subgroup2) of chemotherapy: Subgroup1: every 4 weeks, on day 3 of every second 14-day cycle, and then every 4 weeks starting from the first nivolumab administration. Subgroup2: Every 3 weeks, on day 9 of each 21-day cycle, and then every 4 weeks starting from the second nivolumab administration. Nivolumab for a maximal duration of 2 years: intravenous, starting after the last chemotherapy cycle. Administered as flat dose of 240mg every 2 weeks during 14 weeks, then as flat dose of 480 mg every 4 weeks until the last vaccination. Then, as a maintenance therapy at 480 mg every 4 weeks until appearance of new lesions or unacceptable toxicity.

PEP-DC + Nivolumab + SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Histologically confirmed resected adenocarcinoma of the pancreas (T1-T4, N 0-1-2, minimum 2cm - American Joint Committee on Cancer (AJCC) 8th edition).
• Mixed adenocarcinoma tumors are eligible provided the predominant invasive component of the tumor is adenocarcinoma
• Patients who received or did not receive neo-adjuvant chemotherapy are eligible, both.
• No distant metastasis
• Appropriate amount of tumoral tissue was collected from the cytoreductive surgery and allowed the identification of top 10 personalized peptides (PEP) for preparation of PEP-DC vaccine
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
• Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 21 days prior registration
• Adequate serology defined by the following laboratory results:
• Negative test for human immunodeficiency viruses (HIV)
• Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at pre-screening) are not eligible.
• Patients with past/resolved hepatitis B virus (HBV) infection (defined as having a negative hepatitis B surface antigen (HBsAg) test and a positive antibody to hepatitis B core antigen (anti-HBc) antibody test) are eligible, if hepatitis B virus deoxyribonucleic acid (HBV DNA) test is negative.
• Hepatitis B virus deoxyribonucleic acid (HBV DNA) must be obtained in patients with positive hepatitis B core antibody prior start of study treatment.
• Patients with active hepatitis C are not eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if Polymerase Chain Reaction (PCR) is negative for hepatitis C virus ribonucleic acid (HCV RNA)

You may not qualify if:

• Pregnant or breast-feeding women
• Other malignancy within 2 years prior study enrollment, except for those treated with surgical intervention as curative intent. Patients with a predicted 5-year recurrence-free survival rate equal or more than 95% can be included at the investigator's discretion.
• Current, recent (within 4 weeks prior registration), or planned participation in an experimental drug study.
• Past history with cardiac problem:
• New York Heart Association Class II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior registration. History of stroke or transient ischemic attack within 6 months prior registration.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior registration.
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• Known hypersensitivity to any component of the study treatment
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• The following exceptions are considered:
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study.
• Patients with controlled Type I diabetes mellitus on a stable insulin regimen are eligible
• Psoriasis not requiring systemic treatment.
• Vitiligo.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

CHUV Oncology Department

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Conditions

Neoplasms; Adenocarcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A total of 12 evaluable patients will be recruited. They will receive the same investigational products.

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: November 13, 2020
• Study Start: September 11, 2020
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: February 25, 2025

Record last verified: 2025-02

Locations

CH (1)