CHUV-DO-0011-PC_PEP-DC_2017: 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
Indication :

Adénocarcinome du pancréas


Sponsor :

CHUV


Phase :

I


Traitement :

Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC) + SOC chemotherapy + nivolumab


Spécificités :
  • Non-metastatic surgically resected pancreatic adenocarcinoma
  • Registration should occur within 4 to 12 weeks from surgery

Site :

CHUV


Contact(s) :
Antonia Diklia
PI

CHUV
Oncology

Rue du Bugnon 46
Lausanne
1011

+41 79 556 7902
do.ion.ref@chuv.ch

Primary objective :

To determine the feasibility, safety and tolerability of producing and administering PEP-DC vaccines in the indicated population of patients.
To evaluate immunogenicity by measuring acquired, T cell-mediated immune activating events post vaccination.


Inclusion criteria :
  1. Signed Informed Consent Form
  2. Histologically confirmed resected adenocarcinoma of the pancreas (T1-T4, N 0-1, minimum 2cm - AJCC 8th ed.).
    • Mixed adenocarcinoma tumors are eligible provided the predominant invasive component of the tumor is adenocarcinoma.
    • Both patients who received or did not receive neo-adjuvant chemotherapy are eligible.
  3. No distant metastases.
  4. 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.
  5. Age ≥18 years
  6. ECOG PS of 1 or 2
  7. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol.
  8. Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 21 days prior registration.
  9. Adequate serology defined by the following laboratory results:
    • Negative test for 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 HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible, if HBV DNA test is negative.
    • 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 HCV antibody are eligible only if PCR is negative for HCV RNA.
  10. No measurable tumor lesion according to radiologic criteria (RECIST 1.1).
  11. Recovery from any toxic effects of prior neo-adjuvant therapy to ≤ Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 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:
    • 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.
  12. For women of childbearing potential (WOCBP: sexually mature women who have not undergone hysterectomy, have not been naturally post-menopausal for at least 12 consecutive months or have a serum follicle-stimulating hormone (FSH) < 40 mIU/ml):
    a. Agreement to follow instructions for method(s) of contraception for the couple from screening until 6 months after last vaccine dose, or last chemotherapy treatment, or last nivolumab treatment
    b. WOCBP must have a negative urine pregnancy test within 7 days, before registration. A positive urine test must be confirmed by a serum pregnancy test.
  13. For men and their female partners: agreement to follow instructions for method(s) of contraception for the couple from screening until 7 months after last vaccine dose, or last chemotherapy treatment, or last nivolumab treatment.
  14. Patient is able to undergo leukapheresis

Exclusion criteria :
  1. Pregnant or breast-feeding women.
  2. 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 ≥95% can be included at the investigator’s discretion.
  3. Current, recent (within 4 weeks prior registration), or planned participation in an experimental drug study.
  4. 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).
  5. Known hypersensitivity to any component of the study treatment.
  6. 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.
    • Other conditions not expected to recur in the absence of an external trigger, are permitted to enroll after agreement with the PI.
  7. 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 IV 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.
  8. Administration of a live, attenuated vaccine within 8 weeks before registration:
    • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior registration or at any time during the study.
  9. Dihydropyrimidine dehydrogenase deficiency
  10. 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.
  11. 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.
  12. Patients who have received prior treatment with anti-PD1, anti-PD-L1 or anti-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 (NCI CTCAE Grade 3 and 4).
  13. Treatment with systemic immunostimulatory agents (including but not limited to IFN-alpha, IL-2) for any reason within 4 weeks or five half-lives of the drug, whichever is shorter, prior to registration.
  14. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] 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.
  15. Treatment with Granulocyte colony-stimulating factor within 4 weeks prior registration.