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Single center, phase I/II randomized 2-arm study, evaluating two different vaccination regimens combined with low-dose cyclophosphamide in patients with advanced high grade serous ovarian carcinoma (HGSOC):
In both arms, patients will receive a low dose cyclophosphamide the day before vaccination. Patients will be vaccinated after the end of adjuvant platinum-based chemotherapy, until vaccine exhaustion, disease recurrence, major toxicity or patient withdrawal, whichever is earlier.
Full description
This will be a single center, Phase I/II randomized, two-arm, open-label study to evaluate immunogenicity, safety, and feasibility of two different vaccination regimens combined with low-dose cyclophosphamide in patients with surgically resected, advanced HGSOC. Patients with HGSOC at International Federation of Gynecology and Obstetrics (FIGO) stage III or IV who completed either primary debulking surgery (PDS) or interval debulking surgery (IDS) without residual disease (R0) and who have received at least 6 cycles of adjuvant standard of care (SOC) platinum-based chemotherapy after PDS, or 3 cycles of platinum-based perioperative chemotherapy within an IDS will be eligible for this protocol. A total of 16 patients (8 patients in each arm) will be randomized 1:1 as follows:
In both arms, vaccines will be administered to the patients in combination with low dose cyclophosphamide the day before vaccination. Patients will be vaccinated in the adjuvant setting, with first vaccine injected no more than 18 weeks after the end of SOC platinum-based chemotherapy. Patients will be vaccinated until vaccine exhaustion (which may happen any time after dose 6), disease recurrence, major toxicity or patient withdrawal, whichever is earlier.
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Inclusion and exclusion criteria
Patient enrollment will follow a two-step procedure (at screening before randomization and at assessment after vaccine production) of conditions required for initiating vaccination. Patients must meet all of the criteria described in this section prior to receiving any vaccination.
AT SCREENING:
Inclusion Criteria:
Signed Informed Consent Form
Histologically confirmed diagnosis of advanced, FIGO stage III or IV, high grade serous ovarian carcinoma (HGSOC)
Underwent PDS or IDS without macroscopic residual disease, (R0)
a. Received at least 3 cycles of peri-operative platinum-based chemotherapy before IDS, with the intention to complete at least 6 cycles of peri-operative platinum-based chemotherapy.
OR b. Has completed 6 cycles of adjuvant platinum-based chemotherapy after PDS. In case of toxicity prohibiting 6 cycles of adjuvant platinum-based chemotherapy, a minimum of 4 cycles are required.
Tumor material is available and sufficient for both OC-DC preparation and identification of Top 10 personalized peptides (PEPs) required for PEP-DC vaccine preparation.
Age ≥18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Willing and able to comply with study procedures
Has adequate hematologic and end organ function (kidney, liver and bone marrow), defined by the following laboratory results (complete blood count (CBC), enzyme tests) obtained within 14 days prior to randomization:
Has adequate serology defined by the following laboratory results obtained within 14 days prior to randomization:
Negative test for Human Immunodeficiency Virus (HIV)
Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) are not eligible.
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 HCV Ribonucleic Acid (RNA).
Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol.
Patient is able to undergo leukapheresis
Exclusion Criteria:
A secondary debulking surgery is foreseen.
Prior exposure to anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) and anti-Programmed cell Death 1 (PD1) / anti-Programmed cell Death Ligand (PD-L1) antibodies or other immunotherapy.
Woman of child-bearing potential (WOCBP). By definition, all patients with HGSOC of FIGO stage III to IV who have undergone PDS or IDS, will have undergone total hysterectomy with bilateral salpingo-oophorectomy, and will therefore be women without child-bearing potential. Therefore, no pregnancy tests have to be performed because no WOCBP will be enrolled in this trial.
Breastfeeding women
Other malignancy within 2 years prior to randomization, except for those (for example ductal carcinoma in situ of breast and cervical intraepithelial neoplasia) treated with curative intent. Patients with a predicted 5-year recurrence-free survival rate ≥95% can be included at the investigator's discretion.
Patients with diagnosis of paraneoplastic syndrome.
Current, recent (within 4 weeks prior to randomization), or planned participation in an experimental drug study.
Patient has a serious, non-healing wound, ulcer, or bone fracture.
Patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are excluded. Patients with high bleeding risk or any other hereditary coagulation disorder can be enrolled after careful evaluation, at principal investigator (PI)'s discretion.
Past history with cardiac or vascular problems:
Any other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings 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.
Patient has organ allografts.
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.
Administration of a live, attenuated vaccine within 8 weeks before randomization. Exception: 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 to randomization.
History of immediate hypersensitivity reaction to streptomycin and penicillin.
AT VACCINATION:
Inclusion Criteria:
Has received 6 cycles of platinum-based chemotherapy to first vaccination (minimum of 4 cycles platinum-based chemotherapy in case of severe toxicity and inability to administer all planned 6 cycles).
Confirmation from the Centre des Thérapies Experimentales (CTE) cellular manufacturing facility that at least 6 doses of vaccines have been produced for the patient (for Arm A: PEP-DC1 vaccines, Arm B: OC-DC vaccines) at the CTE cellular manufacturing facility.
Has adequate hematologic and end organ function (kidney, liver and bone marrow), defined by the following laboratory results (complete blood count [CBC], enzyme tests) obtained before start of the study treatment:
Has no evidence of disease confirmed by computerized tomography (CT)-scan of chest/abdomen/pelvis (i.e. tumor-free by CT scan according to RECIST v1.1) and CA 125 Gynecologic Cancer InterGroup (GCIC) criteria (i.e. normal CA 125 blood level) before start of the study treatment.
Has recovered from any toxic effects of prior chemotherapy to ≤ Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.5.0) 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:
Exclusion Criteria:
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 4 weeks prior to first study treatment.
Exceptions:
Patients who are receiving acute, low-dose, systemic immunosuppressant medications (e.g., a 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.
Standard premedication of paclitaxel, docetaxel, nab-paclitaxel, or Caelyx (pegylated liposomal doxorubicin i.e. PLD).
Treatment of late onset nausea and treatment of allergic reaction induced by SOC chemotherapy
Administration of a live, attenuated vaccine within 8 weeks before start of study treatment. Exception: 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 to start of study treatment.
Any other diseases, cardiac, metabolic or other dysfunction, physical examination findings or clinical laboratory findings since the screening visit 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.
Primary purpose
Allocation
Interventional model
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0 participants in 2 patient groups
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Central trial contact
Lana Kandalaft, Pharm D, PhD
Data sourced from clinicaltrials.gov
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