Letrozole for Estrogen/Progesterone Receptor Positive Low-grade Serous Epithelial Ovarian Cancer: a Randomized Phase III Trial (LEPRE Trial)
This is an Italian, multicenter, randomized, open-label phase III trial which will evaluate if Letrozole is superior to standard adjuvant chemotherapy in patients with hormone receptor positive low-grade serous epithelial carcinoma of the ovary (LGSCO). The hypothesis is that letrozole will significantly prolong median progression free survival (PFS) compared with the standard chemotherapy treatment, namely carboplatin AUC 5 and paclitaxel 175 mg/m2.
⁃ I - 1. Age ≥ 18 years. I - 2. Newly diagnosed, low-grade serous carcinoma of the ovary including cancer of fallopian tube and peritoneum (invasive micropapillary serous carcinoma or invasive grade 1 serous carcinoma). This is to be confirmed via nuclear p53 immunohistochemistry testing by a central pathology review performed at the Coordinating Centre.
⁃ I - 3. Immunohistochemically determined positivity (≥ 10%) for ER and/or PgR expression. This is to be confirmed by centralized review.
⁃ I - 4. Patients must have undergone an upfront surgery with maximal cytoreductive effort, with either optimal or suboptimal residual disease status.
⁃ I - 5. Stage III-IV according to 2018 FIGO classification. For proper staging:
• Patients must have undergone contrast-enhanced CT-scan of the chest, abdomen and pelvis within 28 days prior to randomization. If CT-scan is not recommended (e.g. for allergy to contrast agent) MRI or 18F-FDG PET/CT-scan are allowed.
• The imaging evaluation must be accompanied by an anamnestic and physical examination within 14 days prior to randomization.
⁃ I - 6. Postmenopausal, defined as any of the following criteria:
• Patients who underwent bilateral salpingo-oophorectomy;
• Monolateral salpingo-oophorectomy, amenorrhea for 12 or more consecutive months and age ≥60 years;
• Monolateral salpingo-oophorectomy, amenorrhea for 12 or more consecutive months, age \<60 years and FSH and serum estradiol levels within the laboratory's reference ranges for post-menopausal women.
⁃ I - 7. Randomization must take place within 60 days of primary cytoreductive surgery.
⁃ I - 8. Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-1.
⁃ I - 9. To be able to take oral medications.
⁃ I - 10. Adequate bone marrow, hepatic and renal functions as defined below:
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelets ≥ 100,000/mm3
• Hemoglobin ≥ 10.0 g/dL
• Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN)
• ALT and AST ≤ 3.0 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Albumin ≥ 2.8 g/dL
• Serum creatinine ≤ 1.5 x ULN.
⁃ I - 11. Written informed consent obtained prior to any study-specific procedure.