Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer
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|ClinicalTrials.gov Identifier: NCT02283658|
Recruitment Status : Completed
First Posted : November 5, 2014
Results First Posted : March 31, 2020
Last Update Posted : October 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Endometrioid Adenocarcinoma Ovarian Seromucinous Carcinoma Ovarian Serous Cystadenocarcinoma Ovarian Serous Surface Papillary Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Ovarian Germ Cell Tumor Recurrent Primary Peritoneal Carcinoma Undifferentiated Ovarian Carcinoma||Drug: Everolimus Other: Laboratory Biomarker Analysis Drug: Letrozole||Phase 2|
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.
I. Cancer antigen (CA)-125 response, progression-free survival (PFS), overall survival (OS), the confirmed response rate, and adverse events.
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.
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 (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Trial of Letrozole and Everolimus in Relapsed Hormone Receptor Positive Ovarian, Fallopian Tube or Primary Peritoneal Carcinomas|
|Actual Study Start Date :||November 14, 2014|
|Actual Primary Completion Date :||June 15, 2016|
|Actual Study Completion Date :||June 21, 2018|
Experimental: Treatment (everolimus and letrozole)
Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Percentage of Patients Alive and Progression Free Survival at 12 Weeks [ Time Frame: 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.
- Percentage of Participants With CA-125 Response [ Time Frame: Up to 2 years ]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.
- Confirmed Response Rate, Estimated Using RECIST 1.1 Criteria [ Time Frame: Up to 24 weeks ]
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.
- Number of Participants Experiencing Adverse Events [ Time Frame: Up to 30 days post-treatment ]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.
- Overall Suravival(OS) [ Time Frame: Time from registration to death from any cause, assessed up to 2 years ]OS will be estimated using the method of Kaplan-Meier.
- Progression Free Survival (PFS) [ Time Frame: Time from registration to the first of either disease progression or death from any cause, assessed up to 2 years ]
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.
- Expression of Molecular Biomarkers Associated With a Response to Treatment With Letrozole and Everolimus in Patients With Relapsed Ovarian Carcinomas [ Time Frame: 28 days following treatment initiation ]The Fisher's Exact test will be used to measure the associations.
- Response Rates to Letrozole and Everolimus in PDX Avatars [ Time Frame: 28 days following treatment initiation ]Will determine if response rates to letrozole and everolimus in PDX avatars correlate to responses noted in the patients. The Fisher's Exact test will be used to measure the associations.
- Responsiveness of Tumors to Letrozole and Everolimus [ Time Frame: 28 days following treatment initiation ]"Response" will be defined as tumors with at least a 50% reduction in tumor volume at study end. "Unresponsive" will be defined as tumors with less than 10% tumor volume reduction at study end. Intermediate values will be defined as "Stable". Tumor growth curves will be plotted graphically and notated to indicate the outcome status of the originating patients. End of study tumor volumes will be correlated with outcome status of the originating patient as well. The Fisher's Exact test will be used to measure the associations.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02283658
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Gerardo Colon-Otero||Mayo Clinic|