NCT03458221

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
148

participants targeted

Target at P75+ for phase_2

Timeline
5mo left

Started Jan 2023

Typical duration for phase_2

Geographic Reach
1 country

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress89%
Jan 2023Oct 2026

First Submitted

Initial submission to the registry

February 23, 2018

Completed
13 days until next milestone

First Posted

Study publicly available on registry

March 8, 2018

Completed
4.9 years until next milestone

Study Start

First participant enrolled

January 31, 2023

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2026

Last Updated

April 18, 2023

Status Verified

April 1, 2023

Enrollment Period

3.7 years

First QC Date

February 23, 2018

Last Update Submit

April 13, 2023

Conditions

Keywords

Ovarian CancerSignal Transduction PathwayTargeted therapyDrug repurposing

Outcome Measures

Primary Outcomes (1)

  • Progression free survival on matched targeted therapy determined by STP-activity (PFS2) in comparison to the PFS recorded on the therapy administered immediately prior to enrolment (PFS1).

    PFS on matched targeted therapy (PFS2) is defined as the time from start of matched targeted therapy to disease progression, defined by RECIST 1.1 criteria, or death from any cause. PFS on prior therapy (PFS1) is defined as the time from start of the prior treatment to disease progression defined by RECIST 1.1 criteria

    From baseline until the date of documented disease progression or 12 months after the start of targeted therapy.

Secondary Outcomes (10)

  • Proportion of patients with an actionable active pathway for which targeted therapy is recommended in relation to the number of patients who underwent a biopsy.

    From date of biopsy until the date of the result from Multi-disciplinary Tumor Board Meeting, up 14 days after biopsy date.

  • Proportion of patients who receive matched targeted therapy in relation to the number of patients included in each study arm.

    From start date matched targeted therapy until the end of the study enrollment, up to 36 months.

  • Best overall response defined by RECIST 1.1 criteria based on radiological imaging.

    From baseline, radiological evaluation every 12 weeks after the start of targeted therapy until the date of documented disease progression or death, whichever comes first, assessed up to 12 months.

  • One-year survival

    From start date of targeted therapy until date of death or one year follow-up, whichever comes first.

  • Overall survival

    From start date of targeted therapy until the date of death, assessed up to 36 months.

  • +5 more secondary outcomes

Study Arms (4)

A - ER active tumors

EXPERIMENTAL

In case of an aberrantly active Estrogen Receptor (ER) pathway, patients will be treated with Letrozole 2.5mg daily orally until progression of disease.

Drug: Letrozole Oral Product

B - AR active tumors

EXPERIMENTAL

In case of an aberrantly active androgen receptor (AR) pathway, patients will be treated with Bicalutamide 150mg daily orally until progression of disease.

Drug: Bicalutamide Oral Product

C - PI3K active tumors

EXPERIMENTAL

In case of an aberrantly active phosphoinositide 3-kinase (PI3K) pathway, patients will be treated with Everolimus 10mg daily orally until progression of disease.

Drug: Everolimus Oral Product

D - HH and/or PI3K active tumors

EXPERIMENTAL

In case of an aberrantly active Hedgehog (HH) or PI3K pathway, patients will be treated with Itraconazole 300mg twice daily orally until progression of disease.

Drug: Itraconazole Oral Product

Interventions

Letrozole 2.5mg tablet - 2.5mg once dailty until progression of disease.

A - ER active tumors

Bicalutatmide 150mg tablet - 150mg once daily until progression of disease.

B - AR active tumors

Everolimus 10mg tablet - 10mg once daily until progression of disease.

C - PI3K active tumors

Itraconazole 100mg capsule - 300mg twice daily until progression of disease.

D - HH and/or PI3K active tumors

Eligibility Criteria

Age18 Years+
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsOvarian cancer
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Radboudumc

Nijmegen, Gelderland, Netherlands

NOT YET RECRUITING

Catharina Ziekenhuis

Eindhoven, North Brabant, 5623EJ, Netherlands

RECRUITING

Amphia Hospital

Breda, 4818 CK, Netherlands

NOT YET RECRUITING

Maastricht UMC+

Maastricht, 6229 HX, Netherlands

NOT YET RECRUITING

Erasmus MC

Rotterdam, Netherlands

NOT YET RECRUITING

Elisabeth-Tweesteden Hospital

Tilburg, 5022 GC, Netherlands

NOT YET RECRUITING

MeSH Terms

Conditions

Ovarian NeoplasmsNeoplasms, Second Primary

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Targeted therapy based on functional signal transduction pathway activation in patients with recurrent ovarian cancer.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

February 23, 2018

First Posted

March 8, 2018

Study Start

January 31, 2023

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Last Updated

April 18, 2023

Record last verified: 2023-04

Locations