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NUVOLA TRIAL Open-label Multicentre Study

NCT04261465 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 35

Last updated 2020-02-07

No results posted yet for this study

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 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.

Conditions

  • High Grade Serous Ovarian Cancer

Interventions

DRUG

Olaparib

PARP INHIBITOR

DRUG

Paclitaxel

Chemotherapy

DRUG

Carboplatin

Chemotherapy

Sponsors & Collaborators

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    lead OTHER

Principal Investigators

  • Giovanni Scambia, Prof · Fondazione Policlinico Gemelli IRCCS

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-12-01
Primary Completion
2020-12-01
Completion
2022-12-01

Countries

  • Italy

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04261465 on ClinicalTrials.gov