This pilot, phase II trial studies how well everolimus and letrozole work in treating patients with hormone receptor positive ovarian, fallopian tube, or primary peritoneal cavity cancer that has come back. Everolimus and letrozole may stop the growth of tumor cells by blocking some the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. Demonstrate that the combination of letrozole and everolimus leads to a higher percentage of patients who are free of progression at 12 weeks (PFS 12) as compared with that observed in a previously reported phase 2 trial of letrozole alone for relapsed ovarian carcinomas. SECONDARY OBJECTIVES: I. Cancer antigen (CA)-125 response, progression-free survival (PFS), overall survival (OS), the confirmed response rate, and adverse events. TERTIARY OBJECTIVES: I. Identify molecular biomarkers associated with a response to treatment with letrozole and everolimus in patients with relapsed ovarian carcinomas. II. Develop and determine if response rates to letrozole and everolimus in patient derived xenograft (PDX) avatars correlate to responses noted in the patients. OUTLINE: Patients receive everolimus orally (PO) once daily (QD) and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Mayo Clinic in Florida
Jacksonville, Florida, United States
Mayo Clinic
Rochester, Minnesota, United States
Percentage of Patients Alive and Progression Free Survival at 12 Weeks
The percentage of PFS12 successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the exact binomial method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Disease progression in evaluable patients will be defined as one or more of the following: * Any new disease and/or clear progression of evaluable disease; OR * 2 fold elevation in CA-125 from its lowest level (either initial level or nadir, whichever is lowest, since study enrollment) combined with CA-125 elevation confirmed by re-assay at any time.
Time frame: 12 weeks
Percentage of Participants With CA-125 Response
CA-125 response: The key secondary endpoint of the study will be a CA-125 response, defined as a 50% or greater reduction in baseline CA-125. The null hypothesis will be set at CA-125 response rate of 8.3%, based on the response of single agent letrozole, as reported by Bowman et al (7). The treatment of letrozole and everolimus will be considered promising, based on CA-125, if the observed CA-125 response rate is 30% or more.
Time frame: Up to 2 years
Confirmed Response Rate, Estimated Using RECIST 1.1 Criteria
A confirmed tumor response is defined to be either a complete response or partial response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. A complete response (CR) in evaluable patients will be defined as: * Disappearance of any sign of (evaluable) disease, AND * Normalization of CA-125; if CA-125 normalizes, it should be confirmed at any time. A partial response (PR) in evaluable patients will be defined as: * Decrement in CA-125 by \>50%, and * Improvement in any additional evaluable disease (if present) as assessed by the enrolling physician.
Time frame: Up to 24 weeks
Number of Participants Experiencing Adverse Events
The number of patients with adverse events.The maximum grade for each type of adverse event (AE) will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns. These tables are reported in the adverse events section of this report.
Time frame: Up to 30 days post-treatment
Overall Suravival(OS)
OS will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to death from any cause, assessed up to 2 years
Progression Free Survival (PFS)
PFS will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Disease progression in evaluable patients will be defined as one or more of the following: Any new disease and/or clear progression of evaluable disease; OR 2 fold elevation in CA-125 from its lowest level (either initial level or nadir, whichever is lowest, since study enrollment) combined with CA-125 elevation confirmed by re-assay at any time.
Time frame: Time from registration to the first of either disease progression or death from any cause, assessed up to 2 years
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