Niraparib Versus Niraparib-bevacizumab Combination in Women With Platinum-sensitive Epithelial Ovarian Cancer (AVANOVA)
Part 1 (Phase 1): safety and tolerability of bevacizumab-Niraparib combination Part 2 (Randomized Phase 2): to compare Progression-Free Survival (PFS)
PARP inhibitors are active as monotherapy to treat patients with recurrent ovarian cancer; the strongest activity being observed in the platinum sensitive, gBRCAmut subgroup as well as in gBRCAwt, HRD population but also in HRD negative disease.
In the same population there is level one evidence that bevacizumab is beneficial. And a phase two randomized study has indicated that combination of a PARP inhibitor with anti-angiogenic drug is superior to PARP inhibitor alone.
The question is:
Is niraparib combined with bevacizumab superior to niraparib? The comparison of tolerability and efficacy of niraparib-bevacizumab combination against niraparib.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Part 1: AVANOVA1 - A Phase I Study to Evaluate the Safety and Tolerability of Bevacizumab-niraparib Combination Therapy and Determine the Recommended Phase 2 Dose (RP2D) in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Part 2: AVANOVA2 - A Two-arm, Open-label, Phase II Randomized Study to Evaluate the Efficacy of Niraparib Versus Niraparib-bevacizumab Combination in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer.|
- Progression free survival [ Time Frame: 30 months ]This is pick the winer trial. The best arm will be used for phase 3 trial against standard of care.
- Disease Control Rate [ Time Frame: 30 months ]
|Actual Study Start Date:||February 2015|
|Estimated Study Completion Date:||December 2020|
|Estimated Primary Completion Date:||November 2018 (Final data collection date for primary outcome measure)|
Experimental: Niraparib monotherapy
Niraparib mono therapy until progression
Niraparib versus Bevacizumab-Niraparib combo
Experimental: Niraparib-bevacizumab combination
Niraparib-bevacizumab combination therapy until progression
Niraparib versus Bevacizumab-Niraparib comboDrug: Bevacizumab
Part 1: This is a single-centre, phase 1a, open-label, dose-escalation study to evaluate the safety and tolerability of bevacizumab-niraparib combination and determine the RP2D in patients with platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The standard 3+3 design will be used. Part 2: (n=94) This multicenter, prospective, open-label, randomized phase 2 study is evaluating the efficacy of niraparib against niraparib-bevacizumab combination in Women with platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Stratification: Patients are stratified according to:
- HRD status (positive/negative)
- Treatment-Free interval to prior therapy (6-12 months > 12 months) Randomization: 1:1 randomization
Study arms: Patients are randomized to one of the two treatment arms:
Arm 1: Niraparib monotherapy until progression. Arm 2: Niraparib-bevacizumab combination therapy until progression.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02354131
|Contact: Mansoor R Mirza, MD||+45 email@example.com|
|Contact: Louisa Boufercha, MA||+45 firstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Not yet recruiting|
|Boston, Massachusetts, United States|
|Contact: Michael Birrer|
|Copenhagen, Sjaelland, Denmark, 2100|
|Study Chair:||Mansoor R Mirza, MD||Nordic Society for Gynaecologic Oncology|