PEP-DC and OC-DC Vaccine in High Grade Serous Ovarian Carcinoma

NCT05714306 | Withdrawn Phase 1 DMC

• 1 other identifier: CHUV-DO-0005-OVACURE_2017
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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):

• Arm A patients will be vaccinated with a personalized peptide vaccine comprised of autologous monocyte-derived dendritic cells (moDC) loaded with patient-specific peptides (PEP-DC1 vaccine) identified a priori at screening (8 patients);
• Arm B patients will be vaccinated with a personalized tumor lysate vaccine comprising autologous moDC loaded with patient-specific autologous oxidized tumor lysate (OC-DC vaccine), followed by PEP-DC2 vaccine comprised of autologous moDC loaded with up to 10 patient-specific peptides identified midway through OC-DC vaccination (8 patients). 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.

Conditions

Ovarian Carcinoma

Keywords

advanced high grade serous ovarian carcinoma; dendritic cell vaccine

Outcome Measures

Primary Outcomes (1)

• Immunogenicity of OC-DC + PEP-DC vaccine vs. PEP-DC vaccine

  The number of personalized tumor antigen (PTAs) ranked as Top 100 will be identified for each patient before and after treatment and the difference will be compared between the two arms at least at two time-points, first at the end of the 3rd cycle (C3W3), and second, at end of treatment (EOT) visit (if possible at C6W4-W6 also). Specifically, an immunogenicity scoring will be determined as follows: for each of the 100 pre-determined top PTAs, a score will indicate how many peptides either become newly detected (shift from undetectable to detectable) or have a magnitude (frequency of T-cell directed against the epitope) increased by ≥ 2 fold.

  through study completion, an average of 7 years

Secondary Outcomes (5)

• Feasibility of vaccines production and administration in each arm

  3 years after study activation

• Assessment of adverse events in each treatment arm

  From signature of informed consent form (ICF) until 30 days after the last treatment (vaccine/cyclophosphamide)

• Time to progression (TTP)

  5 years

• Disease free survival (DFS) rate

  Evaluated at 12, 24, and 36 months

• Overall survival (OS)

  Evaluated at 5 years

Study Arms (2)

Arm A - PEP-DC1 + low dose cyclophosphamide

EXPERIMENTAL

In arm A, patients will receive PEP-DC1 vaccine in combination with low dose cyclophosphamide.

Biological: PEP-DC1; Drug: Low dose cyclophosphamide

Arm B - OC-DC + low dose cyclophosphamide followed by PEP-DC2 + low dose cyclophosphamide

EXPERIMENTAL

In arm B, patients will receive first, the OC-DC vaccine in combination with low dose cyclophosphamide, then PEP-DC2 vaccine in combination with low dose cyclophosphamide. Finally, patients will be vaccinated with the personalized PEP-DC2 to continue maintenance vaccination.

Biological: OC-DC; Biological: PEP-DC2; Drug: Low dose cyclophosphamide

Interventions

PEP-DC1 BIOLOGICAL

PEP-DC1 vaccine comprises autologous dendritic cells pulsed with personalized peptides detected or predicted a priori (using our current integrated antigen identification methodologies).

Arm A - PEP-DC1 + low dose cyclophosphamide

OC-DC BIOLOGICAL

OC-DC vaccine is an autologous dendritic cell vaccine loaded with autologous oxidized tumor lysate.

Arm B - OC-DC + low dose cyclophosphamide followed by PEP-DC2 + low dose cyclophosphamide

PEP-DC2 BIOLOGICAL

PEP-DC2 comprises autologous dendritic cells pulsed with the peptides detected or predicted after vaccination with OC-DC.

Arm B - OC-DC + low dose cyclophosphamide followed by PEP-DC2 + low dose cyclophosphamide

Low dose cyclophosphamide DRUG

Cyclophosphamide administered on D1 of each cycle, the day prior to each vaccination (Vx) at a dose of 200 mg/m2 intravenously (i.v.)

Arm A - PEP-DC1 + low dose cyclophosphamide; Arm B - OC-DC + low dose cyclophosphamide followed by PEP-DC2 + low dose cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Hemoglobin ≥ 80 g/L
• Neutrophil count ≥ 1.0 x G/L (independently of administration of growth factor within 4 weeks prior to randomisation)
• Platelet count ≥ 100 G/L
• Serum creatinine ≤ 1.5x Institutional Upper Limit of Normal (ULN) or Creatinine Clearance ≥ 40 mL/min.
• Serum bilirubin ≤ 1 ULN (except subjects with Gilbert's syndrome who must have a total bilirubin level of \<3.0 x ULN)

You may not qualify if:

• 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:
• New York Heart Association Class II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to randomization
• History of stroke or transient ischemic attack within 6 months prior to randomization
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Apostolos Sarivalasis, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

• Lana Kandalaft, Pharm D, PhD

  Centre Hospitalier Universitaire Vaudois

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 6, 2023
• Study Start: August 1, 2023
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: March 5, 2025

Record last verified: 2025-03