NCT06785077 Genetic Landscape in Women with Metastatic Ovarian Cancer Before and During Treatment with PARP Inhibitors
| NCT ID | NCT06785077 |
| Status | Recruiting |
| Phase | — |
| Sponsor | European Institute of Oncology |
| Condition | Leukemia, Myeloid, Acute |
| Study Type | INTERVENTIONAL |
| Enrollment | 157 participants |
| Start Date | 2020-10-02 |
| Primary Completion | 2028-04-30 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
This trial targets 157 participants in total. It began in 2020-10-02 with a primary completion date of 2028-04-30.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
Therapy related acute myeloid leukemia and myelodysplasia (t-MN) is a potential late complication of cytotoxic therapy, and it is of particular concern in the treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple cycles of platinum-based chemotherapy during the course of their disease. An epidemiological analysis published in 2011 (Gynecologic Oncology) showed that the overall incidence of t-AML is 0.17%, with a median latency to development of leukemia of 4 years (range 0-27 years). Inhibition of PARP is a potential synthetic lethal therapeutic strategy for the treatment of cancers characterized by specific DNA repair defects, such as those that harbor a BRCA1 or BRCA2 (BRCA1/2) mutation and are therefore deficient in homologous recombination repair. In homologous recombination-deficient tumors, PARP inhibition eliminates an alternative DNA repair pathway essential for maintaining viability, leading to tumor cell death. The estimated prevalence of BRCA1/2 mutations in V2 03/06/2021 2 patients with newly diagnosed high-grade serous ovarian cancer is 20-25% and it might be higher in patients with platinum-sensitive, relapsed ovarian cancer. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. Our hypothesis is that these patients are carriers of clonal hematopoiesis of indeterminate potential (CHIP) before treatment with PARPi. CHIP refers to the presence of clonal population(s) of hematopoietic cells with somatic mutations in genes associated with hematological malignancies (e.g. DNMT3A, ASXL1, TET2, TP53 and others), in the absence of morphological evidence of disease. The proposed study will address the hypothesis that platinum-based chemotherapy may promote the onset of newly developed mutated clones and clonal selection of hematopoietic stem cells harboring somatic mutations. Moreover, the concomitant presence of germline mutations in cancer predisposing genes might increase the pool of pre-existing hematopoietic clones and/or favor the accumulation of subsequent somatic mutations. In this context, the inhibition of PARP-mediated repair of DNA lesions created by chemo or radiotherapy can further favor t-MN development.
Eligibility Criteria
Inclusion Criteria: Women with advanced ovarian cancer in complete or partial remission after surgery and eligible to oral PARP inhibitors as first line in association to chemotherapy or as maintenance therapy. Exclusion Criteria: * Presence of blood cell count abnormalities before PARP inhibitor treatment; * Bone marrow infiltration by EOC cells.
Contact & Investigator
Federica Gigli
PRINCIPAL INVESTIGATOR
Istituto Europeo di Oncologia
Frequently Asked Questions
Who can join the NCT06785077 clinical trial?
This trial is open to female participants only, aged 18 Years or older, studying Leukemia, Myeloid, Acute. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
Is NCT06785077 currently recruiting?
Yes, NCT06785077 is actively recruiting participants. Contact the research team at federica.gigli@ieo.it for enrollment information.
Where is the NCT06785077 trial being conducted?
This trial is being conducted at Milan, Italy.
Who is sponsoring the NCT06785077 clinical trial?
NCT06785077 is sponsored by European Institute of Oncology. The principal investigator is Federica Gigli at Istituto Europeo di Oncologia. The trial plans to enroll 157 participants.
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