Targeted therapy for recurrent ovarian cancer based on signal transduction pathway activity

Signal TrAnsduction Pathway Activity Analysis in OVarian cancER

This study is testing if a new way of choosing targeted treatments based on how active certain pathways in ovarian cancer cells are can help women with recurrent ovarian cancer live longer without their disease getting worse.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 148 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Gynaecologisch Oncologisch Centrum Zuid (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 6 sites (Nijmegen, Gelderland and 5 other locations)
• Trial ID: NCT03458221 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to implement phenotype-guided targeted therapy for patients with recurrent ovarian cancer by utilizing a novel mRNA-based assay to analyze signal transduction pathway (STP) activity. The study will assess the effectiveness of existing targeted drugs, which have manageable toxicity profiles, in patients whose tumors exhibit predominantly active functional STPs. By comparing progression-free survival (PFS) on matched targeted therapy to PFS on prior treatments, the trial seeks to determine if targeted therapy can improve outcomes for these patients. The study will involve multiple centers and include a diverse cohort of women with various histological subtypes of ovarian cancer.

Who should consider this trial

Good fit: Ideal candidates include women over 18 with recurrent ovarian cancer who are platinum-resistant or not yet eligible for standard palliative chemotherapy.

Not a fit: Patients with non-recurrent ovarian cancer or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and quality of life for patients with recurrent ovarian cancer.

How similar studies have performed: Previous studies have shown promise in using targeted therapies based on specific tumor characteristics, suggesting potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

* Female, age \> 18 years
* Patients with recurrent ovarian cancer who meet one of the following criteria:
* Platinum-resistant disease, defined as disease recurrence or progression within six months of last platinum-based chemotherapy or;
* Patient refrains from standard therapy or;
* Asymptomatic patient who is not yet eligible for standard palliative chemotherapy but has an increase of CA125 tumour marker at two consecutive time points 28 days apart with a value of two times nadir above 35 U/ml.
* Progressive disease after at least one prior line of systemic treatment for recurrent disease.
* Radiologically evaluable disease according to RECIST 1.1 criteria (36).
* Ability and willingness to obtain a tumour biopsy after the last course of standard treatment and before start of the study.
* Ability and willingness to provide written and oral consent.
* Able to speak and understand the Dutch language.
* WHO performance status 0-II.
* Adequate renal and liver function to start matched targeted therapy (according to the local clinician).
* Adequate use of contraceptives in case of patients with childbearing potential.

Exclusion Criteria:

* Age \< 18 years.
* Patient is receiving any other anti-cancer therapy (e.g. cytotoxic or targeted drug or radiation) or is chemotherapy naïve. The required wash out period prior to start of matched targeted therapy is at least three weeks.
* Patient is diagnosed with or treated for a second primary tumour (except non-melanoma skin tumour) one year prior to study inclusion.
* Inability to obtain (sufficient) tumour material.
* Previous use of the selected targeted drug as anti-cancer agent.
* Physical condition WHO III-IV.
* Pregnant or lactating women.
* Simultaneous participation in another treatment-related clinical trial.
* Patients with any other clinically significant medical condition which, in the opinion of the local clinician, makes it undesirable for the patient to participate in this study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, severe psychiatric illness, or complicated social situations.

Where this trial is running

Nijmegen, Gelderland and 5 other locations

• Radboudumc — Nijmegen, Gelderland, Netherlands (NOT_YET_RECRUITING)
• Catharina Ziekenhuis — Eindhoven, North Brabant, Netherlands (RECRUITING)
• Amphia Hospital — Breda, Netherlands (NOT_YET_RECRUITING)
• Maastricht UMC+ — Maastricht, Netherlands (NOT_YET_RECRUITING)
• Erasmus MC — Rotterdam, Netherlands (NOT_YET_RECRUITING)
• Elisabeth-Tweesteden Hospital — Tilburg, Netherlands (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Jurgen M Piek, MD, PhD

Conditions: Recurrent Ovarian Cancer, Signal Transduction Pathway Deregulation, Therapy-Associated Cancer, Ovarian Cancer, Signal Transduction Pathway, Targeted therapy, Drug repurposing