NUVOLA TRIAL Open-label Multicentre Study (NUVOLA)
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|ClinicalTrials.gov Identifier: NCT04261465|
Recruitment Status : Recruiting
First Posted : February 7, 2020
Last Update Posted : February 7, 2020
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 BRCA1/2 mutations (gBRCAmut) have an improved survival and higher platinum-sensitivity compared to BRCA1/2 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 BRCA1/2-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] 0.35 [95% CI (confidence interval) 0.25-0.49]; p<0.0001), with the greatest clinical benefit in patients with BRCA mutations (HR 0.18 [95% CI 0.10-0.31]; p<0.0001).
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 Ib/II 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 BRCA1/2 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.
|Condition or disease||Intervention/treatment||Phase|
|High Grade Serous Ovarian Cancer||Drug: Olaparib Drug: Paclitaxel Drug: Carboplatin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||December 1, 2019|
|Estimated Primary Completion Date :||December 1, 2020|
|Estimated Study Completion Date :||December 1, 2022|
Experimental: Paclitaxel Carboplatin Olaparib
Subjects will receive weekly therapy with paclitaxel 60 mg/m2 IV and carboplatin AUC 2 IV for 3 weeks out of 4, and olaparib tablets at the dose of 150 mg bid administered orally for 3 consecutive days (D1-D3), every week for each cycle.
After 3 cycles patients will be evaluated for interval debulking surgery. After surgery they will receive consolidation treatment with paclitaxel and carboplatin according to Investigator's choice
Other Name: Lynparza
- Pathological complete response [ Time Frame: 28 months ]Pathological complete response after 3 cycles of NACT including Olaparib and weekly Carboplatin-Paclitaxel in BRCAmut advanced HGSOC women.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04261465
|Contact: Giovanni Scambia, Proffirstname.lastname@example.org|
|Fondazione Policlinico Gemelli IRCCS||Recruiting|
|Roma, Italy, 00168|
|Contact: Claudia Marchetti, Dr +390630151 email@example.com|
|Principal Investigator:||Giovanni Scambia, Prof||Fondazione Policlinico Gemelli IRCCS|