Ovarian Cancer Treatment With a Liposome Formulated mRNA Vaccine in Combination With (Neo-)Adjuvant Chemotherapy

NCT04163094 | Terminated Phase 1 DMC

• 2 other identifiers: OLIVIA-UMCG-012017-004585-10
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human, open label phase I study in ovarian cancer patients with primary disease eligible for standard-of-care treatment with neo-adjuvant chemotherapy, i.e. 3 cycles carboplatin/paclitaxel, interval surgery and 3 additional cycles carboplatin/paclitaxel. Eight doses of the W\_ova1 vaccine will be administered prior and in combination with the (neo-)adjuvant chemotherapy to induce an anti-tumor immune response. Systemic immune responses are determined using peripheral blood mononuclear cells collected before, during and after vaccinations. Intratumoral accumulation of T-cells recognizing vaccine-encoded TAAs will be determined before vaccination in a tumor biopsy and after the 3 cycles of chemotherapy and the 5th vaccination using tumor tissue derived from interval surgery. \[18F\]FB-IL2 PET-CT will be used for the non-invasive assessment of T-cell activation and correlated to immunohistochemistry tumor tissue data from pre-treatment biopsy and interval debulking surgery

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Change from baseline W_ova1 vaccine antigen-specific T cells in the peripheral blood (systemic induction / expansion of W_ova1 vaccine antigen-specific T cells).

  Number of patients with de novo or increased systemic immune responses (based on the ELISpot Data Analysis Tool 1.0) in the post-vaccination PBMC sample compared to baseline PBMC sample to at least one of the three vaccine antigens

  A PBMC collection is planned at baseline, before start treatment. A further PBMC collection is scheduled after 5 vaccinations before surgery. The post-vaccination PBMC collections are scheduled at approx. 14 days and 2.5 months after final vaccination.

Secondary Outcomes (3)

• Change from baseline W_ova1 vaccine antigen-specific T cells in the tumor (Intratumoral induction / expansion of W_ova1 vaccine antigen-specific T cells)

  Tumor material is collected at baseline by biopsy and compared to tumor material collected during standard-of-care cytoreductive surgery (mid-vaccination, week 12)

• Progression free survival

  Up to 2 years from disease diagnosis

• Safety and tolerability of repetitive doses of the W_ova1 vaccine in combination with carboplatin/paclitaxel

  Up to 28 days after last vaccination

Other Outcomes (1)

• Change from baseline intratumoral visualization of CD25+ T cells using [18F]FB-IL2 PET-CT

  Baseline [18F]FB-IL2 PET-CT compared to [18F]FB-IL2 PET-CT before standard of care cytoreductive surgery (mid vaccination, week 12)

Study Arms (1)

Treatment arm

EXPERIMENTAL

Patients will receive 8 W\_ova1 vaccinations before and during neoadjuvant chemotherapy and adjuvant chemotherapy.

Drug: W_ova1 Vaccine

Interventions

W_ova1 Vaccine DRUG

Patients will be treated with a W\_ova1 vaccine that includes 3 OC TAA RNA-LPX products.

Treatment arm

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary epithelial OC patients with measurable tumor lesions (determined by CT or MRI), who are intended to be treated with neo-adjuvant chemotherapy (carboplatin/paclitaxel), subsequent surgery and adjuvant chemotherapy
• Age ≥ 18 years
• Signed informed consent in accordance with institutional and regulatory guidelines
• Adequate access of the tumor for image-guided biopsy
• Adequate (according to the institutional standards) hematology, liver and kidney function to undergo chemotherapy with carboplatin and paclitaxel
• ECOG-performance status of 0 or 1 at screening
• Current BMI \> 18.5 and no weight loss of \>5% over the past month. Notably, weight loss due to drainage of ascites is not applicable.

You may not qualify if:

• History of a second malignancy except for curatively treated low-stage tumors with a histology that can be differentiated from the epithelial OC type
• History of an autoimmune disease, specifically HAV, HBV, HCV and HIV, or any other systemic intercurrent disease or condition that might affect the immunocompetence of the patient, or treatment with systemic highly immunosuppressive therapy (e.g. transplant recipients or patients who underwent a splenectomy)
• Use of systemic continuous corticosteroid therapy (e.g. prednisone i.v. or p.o. \>7.5 mg / day).
• Pregnancy or breast feeding
• Participation in a trial with another investigational drug within 30 days prior to the enrolment in this trial
• Any condition that in the opinion of the investigator could interfere with the conduct of the trial.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• BioNTech SE: collaborator

Study Sites (1)

UMCG

Groningen, 9713GZ, Netherlands

Location

MeSH Terms

Conditions

Ovarian Neoplasms

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

Study Officials

• H. W. Nijman, MD/PhD

  University Medical Center Groningen, UMCG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a first-in-human, open label phase I study.

Study Record Dates

• First Submitted: November 6, 2019
• First Posted: November 14, 2019
• Study Start: November 25, 2019
• Primary Completion: June 26, 2023
• Study Completion: June 26, 2023
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)