Ignite Creation Date:
2024-05-06 @ 2:16 PM
Last Modification Date:
2024-10-26 @ 1:27 PM
Study NCT ID:
NCT04261465
Status:
UNKNOWN
Last Update Posted:
2020-02-07
First Post:
2020-01-31
Brief Title:
NUVOLA TRIAL Open-label Multicentre Study
Sponsor:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Organization:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study Overview
Official Title:
The NUVOLA TRIAL Neoadjuvant Chemotherapy in Unresectable oVarian Cancer With OLAparib and Weekly Carboplatin Plus Paclitaxel A Phase II Open-label Multicentre Study
Status:
UNKNOWN
Status Verified Date:
2019-11
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NUVOLA
Brief Summary:
Around 15-25 of ovarian cancer OC patients carry germ-line mutation in BRCA1 or BRCA2 genes Recent evidences showed that OC women with germline BRCA12 mutations gBRCAmut have an improved survival and higher platinum-sensitivity compared to BRCA12 naive BRCAwt
Interestingly disease appearance in BRCAmut women is more diffuse than in BRCAwt cases with significantly higher peritoneal tumour load
Nonetheless BRCAmut women additionally show a higher benefit of platinum-based neoadjuvant chemotherapy NACT plus interval debulking surgery compared with BRCAwt women in terms of clinical and pathological responses suggesting that BRCA mutational status might be used as a molecular tool to personalize treatment in high-grade serous ovarian cancer HGSOC patients
OLAPARIB in BRCA mutation carriers Olaparib is a potent oral poly ADP-ribose polymerase PARP inhibitor that causes synthetic lethality in BRCA12-deficient tumour cells In patients with platinum-sensitive relapsed serous ovarian cancer olaparib maintenance treatment significantly improved the duration of progression-free survival compared with placebo hazard ratio HR 035 95 CI confidence interval 025-049 p00001 with the greatest clinical benefit in patients with BRCA mutations HR 018 95 CI 010-031 p00001
Preclinical data suggest that olaparib might also potentiate the efficacy of DNA-damaging chemotherapies including platinum-containing drugs such as carboplatin
In a recent phase IbII study olaparib plus weekly carboplatin and paclitaxel in relapsed ovarian cancer patients was shown to be safe well tolerated and effective especially in germline BRCA mutated gBRCAmut patients
Possibly the addition of a PARP inhibitor olaparib to NACT in HGSOC patient with germline or somatic BRCA12 mutation is able to increase the pathological complete response rate to conventional chemotherapy Combination of intermittent olaparib with weekly carboplatin and paclitaxel might achieve a higher pathological response rate with an acceptable toxicity profile
Interestingly disease appearance in BRCAmut women is more diffuse than in BRCAwt cases with significantly higher peritoneal tumour load
Nonetheless BRCAmut women additionally show a higher benefit of platinum-based neoadjuvant chemotherapy NACT plus interval debulking surgery compared with BRCAwt women in terms of clinical and pathological responses suggesting that BRCA mutational status might be used as a molecular tool to personalize treatment in high-grade serous ovarian cancer HGSOC patients
OLAPARIB in BRCA mutation carriers Olaparib is a potent oral poly ADP-ribose polymerase PARP inhibitor that causes synthetic lethality in BRCA12-deficient tumour cells In patients with platinum-sensitive relapsed serous ovarian cancer olaparib maintenance treatment significantly improved the duration of progression-free survival compared with placebo hazard ratio HR 035 95 CI confidence interval 025-049 p00001 with the greatest clinical benefit in patients with BRCA mutations HR 018 95 CI 010-031 p00001
Preclinical data suggest that olaparib might also potentiate the efficacy of DNA-damaging chemotherapies including platinum-containing drugs such as carboplatin
In a recent phase IbII study olaparib plus weekly carboplatin and paclitaxel in relapsed ovarian cancer patients was shown to be safe well tolerated and effective especially in germline BRCA mutated gBRCAmut patients
Possibly the addition of a PARP inhibitor olaparib to NACT in HGSOC patient with germline or somatic BRCA12 mutation is able to increase the pathological complete response rate to conventional chemotherapy Combination of intermittent olaparib with weekly carboplatin and paclitaxel might achieve a higher pathological response rate with an acceptable toxicity profile
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None