NCT03458221

Signal TrAnsduction Pathway Activity Analysis in OVarian cancER

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 148 (estimated)
• Sponsor: Gynaecologisch Oncologisch Centrum Zuid · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this prospective, parallel-group, cohort study is to implement phenotype-guided targeted therapy based on functional signal transduction pathway (STP) activity in recurrent ovarian cancer patients using a novel mRNA-based assay. Existing targeted drugs with tolerable toxicity profiles are used to investigate the therapeutic value beyond their approved indication, which are deemed beneficial in the select group of patients with a relevant predominantly active functional STP, in order to improve survival and maintain quality of life.

Detailed description

Rationale: Ovarian cancer is one of the most lethal cancers in the world. Standard therapy consists of debulking surgery and chemotherapy. However, despite this aggressive treatment, recurrent disease almost invariably occurs resulting in a five-year survival rate of approximately 30%. Tumour growth is driven by several signal transduction pathways (STPs), and twelve major STPs have been identified as important for carcinogenesis. Currently, several targeted therapy drugs are available and new targeted drugs are being developed. With a newly developed technique, Signal Transduction Activation (STA) analysis, it is possible to assess which pathway is predominant in a specific (ovarian) cancer sample. Therefore, we hypothesize that specifically targeting the predominant STP might impair tumour growth and improve survival. Objective: This study aims to investigate the progression-free survival (PFS) according to RECIST 1.1 criteria on matched targeted therapy by STA-analysis (PFS2) in comparison to the PFS recorded on the therapy administered immediately prior to enrolment (PFS1) in women with recurrent ovarian cancer. Study design: A multi-centre prospective, parallel-group, cohort study. Study population: Recurrent ovarian cancer patients with platinum-resistant disease, patients who refrain from standard therapy and patients who are not yet eligible for standard palliative chemotherapy, including all histological subtypes. Intervention: STA-analysis will be performed on a biopsy taken from the recurrent tumour. Patients will be included if a predominant pathway is identified for which a matched targeted drug is available and deemed adequate by the multidisciplinary tumour board. We will start with targeted therapy in patients with oestrogen receptor, androgen receptor, phosphoinositide 3-kinase and Hedgehog pathway active tumours, since targeted therapy interceding these pathways are easily available with tolerable side effects. Main study parameters/endpoints: The primary outcome is therapy response defined as PFS2/PFS1 ratio according to RECIST 1.1 criteria. Secondary outcomes include the proportion of patients with an actionable active pathway and the proportion of patients receiving matched targeted therapy, best overall response (according to RECIST 1.1 criteria), one-year survival, overall survival, predictive value of STA-analysis results, side effects, quality of life, cost-effectiveness and change in STP activity score comparing the score before treatment and after disease progression.

Conditions

• Recurrent Ovarian Cancer
• Signal Transduction Pathway Deregulation
• Therapy-Associated Cancer

Interventions

Type	Name	Description
DRUG	Letrozole Oral Product	Letrozole 2.5mg tablet - 2.5mg once dailty until progression of disease.
DRUG	Bicalutamide Oral Product	Bicalutatmide 150mg tablet - 150mg once daily until progression of disease.
DRUG	Everolimus Oral Product	Everolimus 10mg tablet - 10mg once daily until progression of disease.
DRUG	Itraconazole Oral Product	Itraconazole 100mg capsule - 300mg twice daily until progression of disease.

Timeline

• Start date: 2023-01-31
• Primary completion: 2026-10-01
• Completion: 2026-10-01
• First posted: 2018-03-08
• Last updated: 2023-04-18

Locations

6 sites across 1 country: Netherlands