Ribociclib and Letrozole in Treating Patients With Relapsed ER Positive Ovarian, Fallopian Tube, Primary Peritoneal, or Endometrial Cancer
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|ClinicalTrials.gov Identifier: NCT02657928|
Recruitment Status : Active, not recruiting
First Posted : January 18, 2016
Last Update Posted : May 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor Positive Postmenopausal Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Recurrent Uterine Corpus Carcinoma||Other: Laboratory Biomarker Analysis Drug: Letrozole Drug: Ribociclib||Phase 2|
I. Demonstrate if the combination of letrozole and ribociclib (LEE011) leads to a higher percentage of patients who are progression free at 12 weeks (PFS 12) as compared with that observed in prior studies with single agent letrozole.
I. Demonstrate if the combination of letrozole and ribociclib (LEE011) leads to a higher cancer antigen 125 (CA-125) response rate in patients with relapsed ER positive ovarian cancers and endometrial cancers as compared to that observed in previously reported single agent letrozole studies.
II. Median 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 ribociclib (LEE011) (in patients with relapsed ovarian carcinomas and endometrial cancers).
II. Develop patient derived xenograft (PDX) avatars on tumors from participants for possible future translational study evaluating a potential correlation between responses in the PDX model to patients' responses.
Patients receive ribociclib orally (PO) daily and letrozole PO daily 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 3-6 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Trial of Ribociclib (LEE011) and Letrozole in ER Positive Relapsed Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinomas, and Endometrial Cancers.|
|Actual Study Start Date :||July 8, 2016|
|Actual Primary Completion Date :||May 21, 2018|
|Estimated Study Completion Date :||July 1, 2021|
Experimental: Treatment (ribociclib and letrozole)
Patients receive ribociclib PO daily and letrozole PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Proportion of patients alive and progression-free at 12 weeks [ Time Frame: At 12 weeks ]The proportion of progression-free at 12 weeks 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.
- CA-125 response, defined as a 50% or greater reduction in baseline CA-125 [ Time Frame: Up to 2 years ]The treatment of letrozole and ribociclib will be considered promising, based on CA-125, if the observed CA-125 response rate is 30% or more.
- Confirmed response rate (complete response or partial response) using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 2 years ]
- Incidence of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days post-treatment ]The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. Adverse events will be analyzed separately by cohort.
- Overall survival [ Time Frame: From registration to death from any cause, assessed up to 2 years ]Overall survival will be estimated using the method of Kaplan-Meier.
- Progression-free survival [ Time Frame: From registration to the first of either disease progression or death from any cause, assessed up to 2 years ]Progression-free survival will be estimated using the method of Kaplan-Meier.
- Creation of patient derived xenograft models for future translational experiments [ Time Frame: 28 days following treatment initiation ]Xenograft will be created on each patient. For patient derived xenograft experiments, response to therapy will be based on tumor volumes measured by ultrasound. 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.
- Molecular biomarkers associated with a response to treatment with letrozole and ribociclib [ Time Frame: Baseline ]Whether response rates to letrozole and ribociclib in patient derived xenograft avatars correlate to responses noted in the patients will be determined. 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): NCT02657928
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|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|