Multicenter, randomized, open label study including patients with advanced HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib.
This is a multicenter, randomized, open label study including patients with advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking. The main scope of the trial is to determine recurrence free survival in patients treated with 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib vs. 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib. Patients will be randomized 1:1 to receive either 3 cycles carboplatin + paclitaxel maintenance therapy with niraparib (Arm A) or 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm B). Randomization will be performed according to the results of the NGS analysis and stratified either to BRCAm independent of LOH or LOHhigh/ BRCAwt, FIGO stage III vs. IV, and countries. In both of the arms, tumor assessments (CT or MRI) will be performed 9-12 weeks after the start of therapy (after 3rd cycle of chemotherapy), after another 9-12 weeks (during maintenance therapy in Arm A and after the 6th cycle of chemotherapy in Arm B) and every 6 months thereafter. The tumor marker CA-125 will be assessed every 12 weeks in both arms. During chemotherapy treatment, clinical visits (blood cell counts, detection of toxicity) occur at least every 3 weeks (depending on the chemotherapy regimen). Serum pregnancy tests for WOCBP occur at least every 4 weeks. During maintenance therapy with niraparib, clinical visits (blood cell counts, detection of toxicity) occur every 4 weeks for the first 11 months and every 12 weeks thereafter. Serum pregnancy tests for WOCBP occur at least every 4 weeks. Complete physical examinations will take place every 12 weeks. Safety will be monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs). About 60 sites in 6 European countries will participate in this study to recruit 640 patients in 36 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
640
We hypothesise that recurrence free survival in patients receiving 3 cycles of chemotherapy followed by maintenance with niraparib is not inferior to 6 cycles of chemotherapy followed by niraparib in advanced HRDpositive high-grade ovarian cancer patients with no residual tumor mass following primary tumor debulking.
Standard chemotherapy as comparator
Universitätsklinik Innsbruck
Innsbruck, Austria
RECRUITINGCliniques Universitaires St. Luc
Brussels, Belgium
ACTIVE_NOT_RECRUITINGUZ Gent
Ghent, Belgium
NOT_YET_RECRUITINGJessa ziekenhuis
Hasselt, Belgium
NOT_YET_RECRUITINGRFS
Recurrence free survival, defined as time from treatment randomization to the earliest date of assessment of first relapse or death by any cause
Time frame: 8 years
Overall survival (OS)
time to event and rate at 3 and 5 years
Time frame: 8 years
TFST
Time to first subsequent treatment
Time frame: 8 years
TWIST (Time Without Symptoms of disease progression or Toxicity of treatment)
at baseline, 3, 6, and 12 months
Time frame: 8 years
PFS2
Time from randomization until the date of second objective disease progression or death by any cause
Time frame: 8 years
Quality of Life (QoL) 1
Patients are asked to answer the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Responses of questions 1-28 are based on a 4-point scale (1=not at all; 4=Very much), with a higher score indicating a high degree of symptomatology and must therefore be assessed negatively. Responses of questions 29 and 30 are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status.
Time frame: 8 years
Quality of Life 2
Patients are asked to answer the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28). Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better symptoms.
Time frame: 8 years
Quality of Life/ Global health status 3
Patients are asked to answer the short version of the SF-36 Health Survey (SF-12). The questionnaire contains a total of 12 questions with different response options. For questions 1, 8 and 12 there are 5 (1=excellent, 5=bad), for question 2-3 there are 3 (1=yes, very restricted, 3=no, not restricted at all) and for questions 9-11 there are 6 response options (1= always, 6 = never). Questions 4-7 can be answered with "Yes" or "No".
Time frame: 8 years
Safety Endpoints - safety of therapy (3 vs. 6 cycles of chemotherapy + niraparib maintenance therapy) according to CTCAE 5.0 criteria will be used as endpoint
The safety objective is to characterize the safety and tolerability of 3 vs. 6 cycles of chemotherapy followed by maintenance therapy with niraparib in advanced HRDpositive high-grade ovarian cancer patients with no residual tumor mass following primary tumor debulking. The following safety parameters will be analyzed: adverse events and serious adverse events graded per NCI CTCAE, Version 5.0 criteria with time to onset/recovery, causality and outcome; changes in laboratory values, vital signs since baseline, treatment discontinuations and reason for discontinuation, death and cause of death etc. concomitant medications will be collected with time and reasons of use. These are routine safety parameters collected and analyzed in Phase II /III oncology trials.
Time frame: 8 years
Cost effectiveness
The objective is to show that less cycles of chemotherapy are as efficient and at the same time less toxic. Additional cycles of chemotherapy significantly increase toxicity and therefore lead to an increase of costs regarding, e.g. in-patient treatment, concomitant medications to treat (S)AEs.
Time frame: 8 years
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UZ Leuven
Leuven, Belgium
ACTIVE_NOT_RECRUITINGUniversity Hospital Ostrava
Ostrava, Czechia
ACTIVE_NOT_RECRUITINGGeneral University Hospital in Prague
Prague, Czechia
RECRUITINGUniversity Hospital Bulovka
Prague, Czechia
ACTIVE_NOT_RECRUITINGUniversitätsklinikum Aachen
Aachen, Germany
RECRUITINGKlinikum Mittelbaden Baden-Baden Bühl
Baden-Baden, Germany
NOT_YET_RECRUITING...and 37 more locations