NCT04627246

Personalized Vaccine with SOC Chemo Followed by Nivo in Pancreatic Cancer

A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Centre Hospitalier Universitaire Vaudois · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Detailed description

This is a single center, single arm, phase Ib trial to evaluate the feasibility, safety, immunogenicity, and efficacy of subcutaneous dendritic cell (DC) vaccine loaded with personalized peptides \[PEP-DC vaccine\] in combination with standard of care adjuvant chemotherapy (subgroup 1: mFOLFIRINOX or subgroup 2: gemcitabine and capecitabine), followed by the antibody nivolumab in patients with non-metastatic surgically resected pancreatic adenocarcinoma. All patients will have previously undergone collection of resected advanced pancreatic tumor tissue under a different research protocol with a separate informed consent. After registration, all patients will receive standard of care chemotherapy: Subgroup 1: intravenous mFOLFIRINOX for twelve 2-week cycles. Subgroup 2: intravenous gemcitabine, and oral capecitabine for eight 21-day cycles. Additionally, all eligible patients will undergo apheresis during the cycle 5 of mFOLFIRINOX (subgroup 1) or the last week of cycle 3 of gemcitabine/ capecitabine (subgroup 2) to collect peripheral blood mononuclear cells (PBMCs) for dendritic cell vaccine production. All patients will receive at least six PEP-DC vaccinations starting concomitant with the 8th cycle (subgroup 1) or the 5th cycle (subgroup 2) of chemotherapy. Subgroup 1: Vaccine will be delivered subcutaneously every 4 weeks, on day 3(+1) of every second 14-day cycle, and thereafter every four weeks starting from the first nivolumab administration. Subgroup 2: Vaccine will be administered subcutaneously every 3 weeks, on day 9 (the day after last gemcitabine infusion) of each 21-day cycle, and thereafter every four weeks starting from the second nivolumab administration. Nivolumab will be administered intravenously over a period of 30 minutes to all patients, for a maximum duration of 2 years, as follows: Subgroup 1: Nivolumab treatment will start after the last cycle of chemotherapy (2 weeks after C12D1) and will be given as flat dose of 240 mg given every 2 weeks, during 14 weeks (2-week cycles). Then it will be administered as flat dose of 480 mg every 4 weeks (4-week-cycles), until the last vaccine dose. Subgroup 2: Nivolumab treatment will start after the last cycle of chemotherapy (3 weeks after C8D1) as flat dose of 240 mg given every 2 weeks, for 14 weeks. Then it will be administered as flat dose of 480 mg every 4 weeks, until the last vaccine dose. Nivolumab treatment should be maintained for at least for 8 weeks after end of the last chemotherapy cycle if vaccination stops earlier. Nivolumab maintenance for both subgroups: After the end of combined treatment period (vaccination plus nivolumab), nivolumab will be given at 480 mg (flat dose) every four weeks to all patients until appearance of new lesions, unacceptable toxicity or until the maximum time for nivolumab treatment (2 year) is reached. Regular physical examination, radiological evaluation and blood testing for safety parameters will be performed according to the schedule during treatment.

Conditions

• Pancreatic Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Autologous Dendritic Cell Vaccine Loaded with Personalized Peptides (PEP-DC vaccine)	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.

Timeline

• Start date: 2020-09-11
• Primary completion: 2028-09-01
• Completion: 2028-09-01
• First posted: 2020-11-13
• Last updated: 2025-02-25

Locations

1 site across 1 country: Switzerland