NUVOLA TRIAL Open-label Multicentre Study

Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study ID
NCT04261465
Phase
PHASE2
Status
Unknown

Conditions

  • High Grade Serous Ovarian Cancer

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Olaparib — DRUG
    PARP INHIBITOR
  • Paclitaxel — DRUG
    Chemotherapy
  • Carboplatin — DRUG
    Chemotherapy

Study Details

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.

Key Dates

Start date
Dec 1, 2019
Status verified
Nov 2019
Primary completion
Dec 1, 2020
Completion
Dec 1, 2022

Study Design

Enrollment
35 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER

Arms

  • 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

Primary Outcome Measure

Pathological complete response [ Time Frame: 28 months ]

Central Contacts

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