This is an international, multicenter, randomized, open, Phase III trial to evaluate the efficacy and safety of carboplatin/paclitaxel/bevacizumab followed by bevacizumab and niraparib compared to carboplatin/paclitaxel followed by niraparib in patients with newly diagnosed advanced ovarian cancer.
Eligible patients will be those patients with newly diagnosed, histologically confirmed, advanced (FIGO stage III/IV, except FIGO stage IIIA2 without nodal involvement) invasive high grade non-mucinous, non-clear cell epithelial ovarian cancer, peritoneal cancer, or fallopian tube cancer, who have either undergone upfront primary surgery or plan to undergo chemotherapy with interval debulking surgery (IDS). In addition, patients should not have any medical contraindications that would exclude treatment with bevacizumab and/or niraparib. All eligible patients will receive the first cycle of chemotherapy (carboplatin area under curve \[AUC\] 5 and paclitaxel 175 mg/m²) as part of Study Run-In-Period (cycle 1). In parallel, central laboratory will determine the breast cancer (BRCA) status in tumor tissue (tBRCA). All patients with a valid central tBRCA test result will be randomized within 3 days prior to day 1 of cycle 2 in a 1:1 ratio in the following treatment arms: Arm 1: Patients will receive further 5 cycles of carboplatin and paclitaxel q21d followed by niraparib once daily for up to a total of 3 years Arm 2: Patients will receive further 5 cycles of carboplatin and paclitaxel plus bevacizumab q21d followed by bevacizumab q21d (for up to 1 year) and niraparib once daily for up to a total of 3 years. The study aims to investigate, if the treatment strategy of carboplatin / paclitaxel / bevacizumab / niraparib is superior to the treatment of carboplatin / paclitaxel / niraparib-Inhibitor in an all-comer population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
970
Area under curve (AUC) 5, intravenous, on day 1 every 3 weeks for 6 cycles
175 mg/m², intravenous, on day 1 every 3 weeks for 6 cycles
7.5 mg/kg or 15 mg/kg (according to local standard), intravenous, on day 1 every 3 weeks starting from cycle 2 in combination with chemotherapy and thereafter for up to 1 year starting from Cycle 7 Day 1
Progression Free Survival (PFS)
Defined as the time from randomization to first progressive disease (PD) or death, whichever occurs earlier. PD is based on investigators assessment using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Time frame: Assessed frequently during the trial until observation of 586 PFS events or three years after Last Patient In, whichever occurs earlier
PFS according to tumor BRCA status
Defined as the time from randomization to first progressive disease (PD) or death, whichever occurs earlier. PD is based on investigators assessment using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Time frame: Assessed frequently during the trial until observation of 586 PFS events or three years after Last Patient In, whichever occurs earlier
Overall Survival (OS)
Defined as the time from randomization to death
Time frame: at every visit during the trial up to 66 months after Last Patient In
Time to First Subsequent Therapy (TFST)
Defined as the time from randomization to the first subsequent treatment or death, whichever occurs earlier
Time frame: at every visit during the trial up to 66 months after Last Patient In
Second Progression (PFS 2)
Defined as the time from randomization to the second progression or death, whichever occurs earlier
Time frame: at every visit during the trial up to 66 months after Last Patient In
Time to Second Subsequent Therapy (TSST)
Defined as the time from randomization to the second subsequent treatment death whichever occurs earlier
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
200 or 300 mg capsules once daily for up to a total of 3 years starting from Cycle 7 Day 1
Klinikum St. Marien Amberg
Amberg, Germany
RECRUITINGKlinikum Augsburg
Augsburg, Germany
RECRUITINGHochtaunus-Kliniken
Bad Homburg, Germany
RECRUITINGHelios Klinikum Berlin-Buch
Berlin, Germany
RECRUITINGOnkologische Schwerpunktpraxis Bielefeld
Bielefeld, Germany
RECRUITINGStädt. Klinikum Brandenburg
Brandenburg an der Havel, Germany
RECRUITINGKlinikum Bremen Mitte
Bremen, Germany
RECRUITINGKlinikum Chemnitz
Chemnitz, Germany
RECRUITINGSt. Elisabeth-Krankenhaus Köln-Hohenlind
Cologne, Germany
RECRUITINGKlinikum Dortmund
Dortmund, Germany
RECRUITING...and 55 more locations
Time frame: at every visit during the trial up to 66 months after Last Patient In
Number of participants with treatment-related adverse events (AE) and/or serious adverse events (SAEs) and/or AEs that led to premature withdrawal of trial treatment and/or interruptions/dose modifications
Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: at every visit during the trial up to safety follow up visit 30 days after last dose
Effects on Quality of Life (QoL)
Questionnaires to be completed by patients and collected frequently during the trial
Time frame: Assessed frequently during the trial up to 66 months after Last Patient In