OV PRECISION:

Tumor-Profiling Based Precision Treatment in Ovarian Cancer, a prospectively randomized controlled Swiss Trial.

Unmet need in Advanced Ovarian Cancer

More than 300,000 women are diagnosed with ovarian cancer (OC) worldwide each year with two third dying of the disease. Ovarian cancer is responsible for more deaths than any other cancer of the female genital tract. The goal of initial surgical treatment is the removal of as much tumor as possible. After this initial treatment, patients receive standard chemotherapy, a combination of two drugs, already developed in the 1990s. If the patient is not stable enough for immediate radical surgery or the disease is very extensive, patients are first treated with 2-3 cycles of chemotherapy in a so-called neoadjuvant setting. This is thought to stabilize the patient and prepare her optimally for surgery. The chemotherapeutic drugs used in OC are carboplatin and paclitaxel, which however can cause considerable and long-lasting side effects, that significantly reduce the quality of life.

There is an urgent need to expand the therapeutic options and provide alternative treatments to women with OC. Instead of treating with only one schedule, a broader spectrum of treatment options is needed. The appearance and outcome of the disease can be highly variable and one treatment option does not fit all patients.

⇒ A personalized treatment should be based on the unique cellular composition, the microenvironment and molecular background of the tumor and on the patient herself.

Approximately 50% of OC have a defective DNA repair mechanism via homologous recombination (homologous recombination deficiency, HRD). These HRDpos patients respond very good to carboplatin and to so-called PARP inhibitor drugs, resulting with a better overall survival (OS) (2,3). In contrast, a HRD negative (HRDneg) status in the remaining 50% of patients with OC is an established marker of poor prognosis, associated with primary carboplatin resistance and shorter survival rates (PFS 11.5 months (4)). To date, no treatment has shown a survival benefit for this patient group, let alone controlling or relieving symptoms. 

⇒The OV Precision trial explicitly studies this group of HRD negative (HRDneg) patients (5). Our aim is to change the outcome of these patients by identifying personalized treatment options at initial diagnosis.

Tumor Profiling (TP) and patient-specific treatment in OV Precision

For the Tumor Profiling (TP) testing in this clinical trial  which will be done in a cooperation with the Tumor Profiler Center TPC, we will incorporate the previously used technologies (TuPro Trial; BASEC: 2018-02052 & (1)) to provide real-life treatment decision support. Turn-around-time and feasibility are important measures as the patient may already be symptomatic and treatment needs to be started without delay. We will therefore have technologies in the fast decision loop (Figure 1) and technologies in a slower analysis loop. In our previous Tumor Profiler study, we have assumed that in 81% of newly diagnosed HRDneg OC patients, an alternative registered drug would be more effective than the standard chemotherapy.

⇒ OV Precision will result in patient-specific treatment quite likely improving the patient’s prognosis as well as reducing unnecessary side effects.

The OV Precision trial will validate the hypothesis that 81% of patients with HRDneg would benefit from another than the standard of care chemotherapy treatment. We will recruit 120 (HRDneg) patients over a two-year period. For this we will include newly diagnosed epithelial OC and carcinosarcoma patients with a pathologically confirmed FIGO Stage IIIC and IV with no immediate need of systemic or surgical treatment at time of diagnosis or within the first 2 weeks of diagnosis. Overall operability is sought after 2 cycles of chemotherapy or 42 days of treatment. Initially, all included patients independent of HRD status will be analyzed, using treatment-naïve tumor material. Results from all TP technologies are merged with routine clinical and diagnostic data and summarized in a visual Molecular Summary Report (MSR) (1). On this basis, a personalized treatment recommendation is made in the study-specific molecular tumor board, which is composed among others of medical and gynecological oncologists.

⇒The patient-tailored treatment recommendation can potentially lead to downscaling of treatment, which can subsequently reduce side effects and equally improve the survival of the patient.

Figure 1: OV Precision: Tumor Profiling for patient tailored treatments

By random principle with a 50:50 chance (randomization) the patients will be divided into 2 arms. In the experimental arm, the treatment recommendation is presented to the treating physician and the patient for discussion and potential implementation. After completion of the treatment, the TP analysis is performed again to prove the effect of the treatment at the molecular level. All patients will receice Standard of Care (SOC) treatment after the End of the Study (EOS).

Figure 2: OV Precision Trial Design; R=Randomization
*Personalized care: Choice of treatment at the discretion of oncologist and individual patient
°Dependent on operability of patient

Study duration

The study is going to start in 2023 and the estimated study duration for the main investigational plan is two years. Analysis of data and publication will take another year.

Investigators & Study Centres

OV Precision trial is planned to recruit with at least 10 Swiss sites, mostly the top Swiss recruiters of the international ENGOT-ov54/Swiss-GO-02/MATAO, another Swiss-GO Trial. The list of selecetd study centers with confirmed participation will be updated regularly below. 

For more information, please contact Swiss GO Trial Group under:Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein.

Funding: Donations, Grants and Sponsoring

The study is fully funded. We thank our sponsors and our partner TPC:

GCP Statement

This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) as well as all national legal and regulatory requirements.

References

(1) Irmisch et al, 2021
(2) Colombo N et al., 2019
(3) Ledermann JA et al., 2018
(4) Swisher et al., 2021
(5) Yann et al., 2022