Personalized Vaccine With SOC Chemo Followed by Nivo in Pancreatic Cancer

  • STATUS
    Recruiting
  • End date
    Sep 10, 2028
  • participants needed
    12
  • sponsor
    Centre Hospitalier Universitaire Vaudois
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Updated on 10 July 2022
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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

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 intravenous administration will start after the last cycle of chemotherapy (for Subgroup1: 2 weeks after C12D1 and for Subgroup2: 3 weeks after C8D1) 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.

Details
Condition Pancreatic Adenocarcinoma
Treatment Autologous Dendritic Cell Vaccine Loaded with Personalized Peptides (PEP-DC vaccine)
Clinical Study IdentifierNCT04627246
SponsorCentre Hospitalier Universitaire Vaudois
Last Modified on10 July 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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)
No measurable tumor lesion according to radiologic criteria (New Response Evaluation
Recovery from any toxic effects of prior neo-adjuvant therapy to less than Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 except for toxicities described below, as long as they do not put at risk the patient's condition and do not require systemic immunosuppressive steroids at any dose, including but not limited to
Criteria in Solid Tumours 1.1 (RECIST 1.1))
Fatigue
Alopecia
Skin disorders
Stable neuropathy
Endocrinopathies requiring replacement treatment
Note: For other medical conditions, or for any other toxicity with a higher grade but
controlled by adequate treatment, prior discussion and agreement with the principal
investigator is mandatory
Note: Patients may have undergone surgical procedures within the past 3 weeks, as long as
all toxicities have recovered to grade 1 or less
For women of childbearing potential (sexually mature women who have not undergone a
hysterectomy, have not been naturally post-menopausal for at least 12 consecutive
months or have a serum follicle-stimulating hormone (FSH) less than 40 milli
Patient is able to undergo leukapheresis
international unit per milliliter (mIU/ml)
Agreement to follow instructions for methods of contraception for the couple from
screening until 6 months after last vaccine dose, or last chemotherapy treatment
or last nivolumab treatment
Women of childbearing potentia must have a negative urine pregnancy test within 7
days, before registration. A positive urine test must be confirmed by a serum
pregnancy test
For men and their female partners: agreement to follow instructions for methods of
contraception for the couple from screening until 7 months after last vaccine dose, or
last chemotherapy treatment, or last nivolumab treatment

Exclusion Criteria

Pregnant or breast-feeding women
Past history with cardiac problem
New York Heart Association Class II or greater congestive heart failure
Known hypersensitivity to any component of the study treatment
The following exceptions are considered
Other malignancy within 2 years prior study enrollment, except for those treated with
surgical intervention as curative intent. Patients with a predicted 5-year
Psoriasis not requiring systemic treatment
recurrence-free survival rate equal or more than 95% can be included at the
Vitiligo
investigator's discretion
Current, recent (within 4 weeks prior registration), or planned participation in an
experimental drug study
Administration of a live, attenuated vaccine within 8 weeks before registration
History of myocardial infarction or unstable angina within 6 months prior
Dihydropyrimidine dehydrogenase deficiency
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)
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
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
Other conditions not expected to recur in the absence of an external trigger, are
permitted to enroll after agreement with the principal investigator
Severe infections within 8 weeks prior registration including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia or
signs or symptoms of infection requiring oral or intravenous antibiotics within 8
weeks prior registration
Patients receiving routine antibiotic prophylaxis (e.g., to prevent chronic
obstructive pulmonary disease exacerbation or for dental extraction) are eligible
Influenza vaccination should be given during influenza season only (approximately
October to March). Patients must not receive live, attenuated influenza vaccine within
weeks prior registration or at any time during the study
Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications
Any serious or uncontrolled medical disorder or active infection that, in the
opinion of the investigator, may impair the ability of the subject to receive
protocol therapy and comply with study visits and procedures
Patients who have received prior treatment with anti-programmed cell death 1
(PD1), anti-programmed death ligand 1 (PD-L1) or anti-cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4) may be enrolled, provided at least 5
half-lives have elapsed from the last dose to the first dose of nivolumab and
there was no history of severe immune-mediated adverse effects from such therapy
(National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE) Grade 3 and 4)
Treatment with systemic immunostimulatory agents (including but not limited to
interferon-alpha, interleukin-2) for any reason within 4 weeks or five half-lives
of the drug, whichever is shorter, prior to registration
Treatment with systemic immunosuppressive medications (including but not limited
to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate
thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior
registration
Patients who are receiving acute, low-dose, systemic immunosuppressant medications
(e.g., an one-time dose of dexamethasone for nausea) or physiologic replacement doses
(i.e., prednisone 5-7.5 mg/day, or other) for adrenal insufficiency may be enrolled in
the study
The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is
allowed
Treatment with Granulocyte colony-stimulating factor within 4 weeks prior
registration
Treatment with K-vitamin antagonists such as warfarin unless it is switched to
another type of anticoagulant treatment, if the patient is assigned to receive
capecitabine
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