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…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
- Ovarian and fallopian tube disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is therapy response defined as PFS2/PFS1 ratio according to
RECIST 1.1 criteria.
Secondary outcome
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 overall survival
and overall survival, predictive value of STA-analysis results, side effects,
quality of life, cost-effectiveness and change in pathway activity score after
disease progression compared to the pathway activity score before the start of
targeted therapy.
Background summary
Ovarian cancer is one of the most lethal cancers in the world due to late stage
disease at diagnosis. 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.
Study 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
Multicentre prospective cohort study with multiple stepwise executed treatment
arms.
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.
Study burden and risks
Patients could experience potential benefits when they participate in this
study, namely, that the strategy of selecting patients for treatment with
targeted therapy based on STA-analysis will result in improved PFS, by tumour
regression or stabilization, with maintaining quality of life. The potential
risks for patients are the side effects of the targeted drug(s) used and
thereby diminished quality of life, and the risk of ineffective treatment. The
extra burden that comes with participation in this study consists of a
histological biopsy with risk of pain and haemorrhage. This procedure is
considered safe as there is ample experience with performing biopsies in
patients with recurrent ovarian cancer.
Michelangeloaan 2
Eindhoven 5623EJ
NL
Michelangeloaan 2
Eindhoven 5623EJ
NL
Listed location countries
Age
Inclusion criteria
- Age 18 years or older
- Patients with recurrent ovarian cancer who meet one of the following criteria:
1. Platinum-resistant disease or;
2. Patients refrains from standard therapy or;
3. Asymptomatic patients who are not yet eligible for standard palliative
chemotherapy but have an increase of CA125 tumour marker at two consecutive
timepoints 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.
- 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.
- Contra-indication for the use of the matched targeted therapy.
- 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005091-36-NL |
| Other | NCT03458221 |
| CCMO | NL77022.100.21 |