Personalized Vaccine With SOC Chemo Followed by Nivo in Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT04627246|
Recruitment Status : Recruiting
First Posted : November 13, 2020
Last Update Posted : November 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Adenocarcinoma||Biological: Autologous Dendritic Cell Vaccine Loaded with Personalized Peptides (PEP-DC vaccine)||Phase 1|
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 (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 consisting of intravenous gemcitabine, and oral capecitabine for eight 21-day cycles. Additionally, all eligible patients will undergo apheresis during the last week of cycle 3 of standard of care chemotherapy 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 5th cycle of chemotherapy. 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 intravenous administration will start three weeks after the last cycle of chemotherapy and will be given as a flat dose every 2 weeks during the vaccination period until the last vaccine dose or at least 8 weeks after the end of the last chemotherapy cycle if vaccination stops earlier.
Regular physical examination, radiological evaluation and blood testing for safety parameters will be performed according to the schedule during treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||A total of 12 evaluable patients will be recruited. They will receive the same treatment.|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||September 11, 2020|
|Estimated Primary Completion Date :||September 2028|
|Estimated Study Completion Date :||September 2028|
Experimental: PEP-DC + Nivolumab + SOC
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)
SOC: gemcitabine intravenously, on days 1 and 8 of each 21-day cycle, and capecitabine orally for 14 days of a 21-day cycle. Total: 8 cycles.
PEP-DC vaccine: At least 6 vaccinations starting with the 5th cycle of chemotherapy. Vaccine will be administered subcutaneously every 3 weeks, on day 9 (the day after last gemcitabine infusion) of each 21-day cycle (cycle 5, 6, 7 and 8), and thereafter every 4 weeks starting from the second nivolumab administration.
Nivolumab: it will be administered intravenously, starting 3 weeks after the last chemotherapy cycle and will be given as a flat dose of 240mg every 2 weeks during the vaccination period until the last vaccine dose or at least for 8 weeks after the end of last chemotherapy cycle if vaccination stops earlier. Afterwards, it will be given as a maintenance therapy without vaccine at 480 mg (flat dose) every 4 weeks until appearance of new lesions or unacceptable toxicity for a maximum of 2 years.
- Number of cases for which vaccine is produced [ Time Frame: 3 years after study activation ]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 6 PEP-DC vaccines for a patient) among the enrolled patients and number of patients who receive at least one dose of vaccine
- Assessment of adverse events [ Time Frame: 3 years after study activation ]Collection of adverse events and serious adverse events, treatment limiting toxicities and assessment of immunogenicity
- Relapse free survival [ Time Frame: 8 years ]Time from enrolment (registration) date until one of the following events: a. patients disease-free at inclusion, until first date of documented progression, b. patients with non-measurable lesions at inclusion, until first date of documented progression, c. death
- Overall survival [ Time Frame: 8 years ]Time from enrolment (registration) date to date of death due to any cause, or last patient contact. For living patients, the date of most recent clinic visit or a phone or email contact will be employed to document the overall survival time.
- Gene analysis of immunological response [ Time Frame: 8 years ]The assessment of the interactions between tumor cells and the immune system within the tumor microenvironment will be performed by gene expression quantification using with multiplex gene expression profiling.
- Cell analysis of immunological response [ Time Frame: 8 years ]The assessment of the interactions between tumor cells and the immune system within the tumor microenvironment will be performed by cell quantification using with multi-parametric single-cell cytometry and single cell RNA sequencing analysis
- Evaluation of tumor marker carbohydrate antigene 19-9 (CA19-9) or carcinoembryonic antigen (CEA) kinetics [ Time Frame: 8 years ]Measurement of tumoral markers by blood analysis
- Correlation between immune-related adverse events and relapse-free survival [ Time Frame: 8 years ]Number of immune-related adverse events using the CTCAE v.4.03 correlated with relapse-free survival (time in months)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04627246
|Contact: Lana Kandalaft, PharmD, PhD||0041 21 314 78 firstname.lastname@example.org|
|Contact: Antonia Digklia, MD||0041 21 314 79 email@example.com|
|CHUV Oncology Department||Recruiting|
|Lausanne, Vaud, Switzerland, 1011|
|Contact: Antonia Digklia, MD 0041 21 314 79 28 firstname.lastname@example.org|