OV Precision: Study Examining the Benefit of a Tumor- and Patient-specific Cancer Therapy

Official title

OV PRECISION: A Randomized Controlled Swiss Trial Examining the Benefit of a Tumor- and Patient-specific Cancer Therapy in Ovarian Cancer.

Overview

The long-term goal of this research project is to demonstrate whether HRD negative (HPDneg) patients benefit when additional multi-modal biological tumor information is incorporated into the molecular tumor board (mTB) treatment recommendation process.

Detailed description

Homologous recombination proficient (HRP) or HRD negative (HRDneg) Ovarian Cancer (OC) patients have a poor outcome equivalent to platinum-resistant patients (PFS 11.5 month). Given standard of care chemotherapy is not ideal for 50% of EOC and this patient population urgently needs alternative treatment options tailored to their individual tumor profile. Treatment options for the heterogeneous HRDneg patient group are scarce and mainly focus on symptom control and palliation, delaying time to symptomatic progression, and improving QoL.

Therefore, trials at initial diagnosis, when the patient can still be cured and is treatment naïve, are urgently needed.

The intervention studied is a personalized treatment recommendation by a specialized molecular tumorboard. This recommendation is based on a molecular summary report (MSR), which is created by multi-modal Tumor Profiling (TP), i.e., molecular analysis of clinical specimens, obtained from the individual participant.

TP, a technology platform of several precision-cancer profiling domains established by the TPC (= Tumor Profiler Center, Switzerland). It combines and rates the most efficient drugs/ experimental treatments for an individual ovarian cancer patient independent of standard of care (SOC).

The usability in clinical practice of this recommendation will be tested. It should support the clinical decision of the treating oncologists and patients to choose the best possible therapy for the individual patient. Treatment recommendations on the most appropriate molecular-based treatment for the individual patient are formulated based on the expertise and experience of the mTB board members. Additionally, a MSR from a validated TP technology platform can serve as further guidance in the tumorboard. However, the final decision on initial treatment remains at the discretion of the treating physician and the patient.

OV Precision is a multicenter randomized (1:1) controlled trial comparing a personalized treatment recommendation at the discretion of the treating physician in agreement with the patient versus SOC without receiving a mTB recommendation.

The study will be divided into two phases: an initial diagnostic phase, in which presumed eligible patients will be recruited into the study, HRD status will be determined, and tumor profiling will be performed in HRDneg patients with a confirmed diagnosis. Eligible patients will be randomized and treated according to their group allocation in the second phase (treatment phase).

The study duration is planned for 3 years including analysis: Two years of recruitment (starting from 09/2024), final analysis of the focal endpoints and end of the study 10 weeks after inclusion of the last patient (12/2026). Study analysis and publication should be completed approximately one year later (12/2027).

Interventions

• Other Treatment recommendation by molecular tumorboard (mTB) based on tumor profiling
  The intervention studied is a treatment recommendation by a specialized molecular tumorboard (mTB). This recommendation is based on an MSR which is created by TP, i.e., molecular analysis of clinical specimens, obtained from the individual participant. TP, a technology platform of several precision-cancer profiling domains, combines and rates the most efficient drugs/ experimental treatments for an individual ovarian cancer patient independent of standard of care. The usability in clinical pract
• Drug Carboplatin / Paclitaxel Chemotherapy
  2 cycles of chemotherapy with carboplatin AUC5 3-weekly and paclitaxel 175 mg/m2 3-weekly or carboplatin AUC2 weekly and Paclitaxel 60-80mg/m2 weekly

Primary outcome measures

• Focal Outcome Measure (FOM) 1 of pilot study: Proportion of patients for whom the molecular Tumor Board (mTB) considers a different treatment option [Time frame: 2-3 weeks]
• FOM 2 of pilot study: Investigation whether the treating oncologist feels better supported by the mTB recommendation considers the additional biological tumor information than by the standard of care where such information is not considered. [Time frame: 2-3 weeks]
• FOM 3 of pilot study: Investigation of different treatment decisions by the patient and the treating oncologist. [Time frame: 4 weeks]
• FOM 4 of pilot study: Preliminary estimate of the actual patient benefit of the intervention in terms of a number of patient-relevant outcomes. [Time frame: 10 weeks]

Eligibility criteria

Inclusion criteria

• Newly diagnosed EOC (adenocarcinoma of the ovary, peritoneum, and fallopian tube) and carcinosarcoma patients with a suspected FIGO Stage III and IV
• No immediate need of systemic or surgical treatment at time of and until 2 weeks after diagnosis
• Envisaged surgical candidate for interval debulking after 2 cycles of treatment
• Willing and able to attend the visits, to understand the purpose of the trial and all trial-related procedures
• ECOG 0-2
• Written informed consent according to national legal and regulatory requirements prior to any project specific procedures

Exclusion criteria

• Elevated liver enzymes (double of normal range: ASAT > 68 U/l; ALAT > 82 U/l; GGT > 80 U/l)
• Elevated creatinine (double of normal range: >120 mmol/l))
• ECOG ≥3
• Pregnant or lactating women
• Any other malignancy within the last 5 years which has an impact on the prognosis of the patient
• Inability to swallow tablets
• Concurrent participation in another clinical trial on the same indication
• Any other serious underlying medical, psychiatric, psychological, familial, or geographical condition, which in the judgment of the sponsor-project leader may interfere with the project or affect patient compliance

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Switzerland · 7 centers

• Kantonsspital Baden AG — Baden
• Universitätsspital Basel — Basel
• HOCH Health Ostschweiz Kantonsspital St.Gallen — Sankt Gallen
• Thurgau AG Frauenfeld / Münsterlingen — Frauenfeld
• Inselspital Bern (University Hospital for Medical Oncology) — Bern
• HFR-Fribourg- Hopital Cantonal — Fribourg
• University Hospital Zurich — Zurich

Identifiers

NCT: NCT06466382 · Swiss-GO-08/ OV Precision

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗