A Phase II Trial of Ribociclib (LEE011) Plus Letrozole in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube or Peritoneum
The study evaluates the response to treatment with Ribociclib and Letrozole in patients with low grade serous cancer of the ovary, fallopian tube or peritoneum.
Ribociclib and letrozole
- 2Age > 18 years at time of study entry.
- Willingness and ability to comply with study and follow-up procedures.
- Histological confirmation of diagnosis of low-grade serous carcinoma of ovary, fallopian tube or peritoneum; Original diagnosis of de novo low-grade serous carcinoma or Original diagnosis of serous borderline tumor with subsequent diagnosis of low-grade serous carcinoma.
- In order to prevent inclusion of patients with high-grade serous carcinoma, diagnosis of low-grade serous carcinoma will be verified as part of screening review by a gynecologic pathologist. Tissue for confirmation can be from primary tumor or recurrence.
- Patient must have recurrent, measurable disease by RECIST v1.1.
- There are no restrictions on number of prior therapies.
- Patient cannot have previously received a prior cyclin dependent kinase inhibitor (CDKi). Patients who were treated with letrozole or another aromatase inhibitor for other indications must have not taken the drug for 6 months prior to initiating letrozole for this trial and may not have progressed on treatment.
- Patients must not have remaining ovarian function to be included. In women who have at least one retained ovary, menopause must be confirmed with laboratory confirmation. Women who have ovarian function are eligible but must be placed on hormonal suppression. Menopause must be confirmed with laboratory confirmation, to include an estradiol level as this is assessed within 8 weeks of patient having been on tamoxifen.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade ≤ 1.
- Patient has adequate bone marrow and organ function as defined by the following laboratory values at screening:
- Absolute neutrophil count ≥1.5 × 109/L
- Platelets ≥100 × 109/L
- Hemoglobin ≥9.0 g/dL
- Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication
- INR ≤1.5
- Serum creatinine <1.5 mg/dL or creatinine clearance ≥50 mL/min
- In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN. If the patient has liver metastases, ALT and AST <5 x ULN
- Total bilirubin < ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome.
- Patient with available standard 12-lead ECG with the following parameters at screening:
- QTcF interval at screening <450msec (using Fridericia's correction)
- Resting heart rate 50-90bpm
- Must be able to swallow ribociclib and letrozole capsules/tablets.