Description:
The purpose of this study is determine if the triplet combination of ribociclib, everolimus and exemastane is effective in the treatment of locally advanced/metastatic breast cancer following treatment with a CDK 4/6 inhibitor
Clinical Trials /
Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor.
NCT02732119
Related Conditions:
- Breast Carcinoma
Recruiting Status:
Completed
Phase:
Phase 1/Phase 2
Trial Eligibility
Document
Title
- Brief Title:Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor.
- Official Title:A Phase I/II, Single Arm, Open-label Study of Ribociclib in Combination With Everolimus + Exemestane in the Treatment of Men and Postmenopausal Women With HR+, HER2- Locally Advanced or Metastatic Breast Cancer Following Progression on a CDK 4/6 Inhibitor
Clinical Trial IDs
- ORG STUDY ID: CLEE011XUS29
- NCT ID: NCT02732119
Trial Conditions
- Breast Cancer
Trial Interventions
| Drug | Synonyms | Arms |
|---|---|---|
| Ribociclib | ribociclib + everolimus + exemestane | |
| Everolimus | ribociclib + everolimus + exemestane | |
| Exemestane | ribociclib + everolimus + exemestane |
Trial Purpose
The purpose of this study is determine if the triplet combination of ribociclib, everolimus and exemastane is effective in the treatment of locally advanced/metastatic breast cancer following treatment with a CDK 4/6 inhibitor
Detailed Description
The purpose of the phase I dose escalation part of this study is to estimate the MTD(s) and/or identify the RP2D of the combination treatment of ribociclib+ everolimus + exemestane when dosed continuously in adult men and postmenopausal women with HR+ HER2-negative advanced breast cancer resistant to the non-steroidal aromatase inhibitors, fulvestrant or tamoxifen.
The purpose of the phase II portion of this trial will be to evaluate the anti-tumor activity of exemestane, everolimus and ribociclib triplet following progression on a CDK 4/6 inhibitor. This part of the study will be conducted using a Simon's optimal two-stage design.
Trial Arms
| Name | Type | Description | Interventions |
|---|---|---|---|
| ribociclib + everolimus + exemestane | Experimental | ribociclib with everolimus and exemestane daily |
|
Eligibility Criteria
Inclusion Criteria:
- Adult men and women
- Patient has a confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory and has HER2-negative breast cancer
- Patient must have either measurable disease by RECIST 1.1 or bone lesions in absence of measurable disease.
- ECOG Performance Status 0 - 1
- Disease refractory to either, AI, tamoxifen or fulvestrant
- Previously treated on any CDK 4/6 inhibitor.
- Patient has adequate bone marrow and organ function.
Exclusion Criteria:
- Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
- Patient has received more than one line of chemotherapy for advanced disease.
- Previous treatment with mTOR inhibitors, or exemestane for advanced disease.
- Progressed on more than one CDK 4/6 inhibitor
- Patient with CNS involvement unless they are at least 4 weeks from prior therapy completion.
- Clinically significant, uncontrolled heart disease and/or recent cardiac events.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Both |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase I: Maximum Tolerated Dose (MTD) and/or the Recommended Phase II Dose (RP2D) for the triplet combination |
| Time Frame: | up to 6 months |
| Safety Issue: | No |
| Description: |
Secondary Outcome Measures
| Measure: | Phase II: Centrally assessed progression Free Survival (PFS) |
| Time Frame: | up to approximately 12 months |
| Safety Issue: | No |
| Description: |
| Measure: | Phase II: Overall Survival (OS) |
| Time Frame: | Up to approximately 36 months |
| Safety Issue: | No |
| Description: | This is defined as the time from treatment initiation with study treatment until death as a result of any cause. |
| Measure: | Phase II: Overall Response Rate (ORR) |
| Time Frame: | Up to approximately 12 months |
| Safety Issue: | No |
| Description: | Overall response rate (ORR) defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST 1.1 |
| Measure: | Phase II: Duration of Overall Response (DOR) |
| Time Frame: | Up to approximately 12 months |
| Safety Issue: | No |
| Description: | Duration of Overall Response defined as the time between the initial response to the treatment with the combination of ribociclib+everolimus+ exemestane, and subsequent disese progression or recurrence. |
| Measure: | Phase II: Time to definitive deterioration of ECOG performance status in one category of the score |
| Time Frame: | Up to approximately 12 months |
| Safety Issue: | No |
| Description: | Time to definitive deterioration of ECOG performance status in one category of score is defined as the time from the date of randomization to the date of event, which is defined as at least one score lower than the baseline. |
Trial Keywords
- HR-positive
- HER2-negative
- Advanced breast cancer
- LEE011
- ribociclib
- everolimus
- Afinitor
- exemestane
- Aromasin
- CDK
- CDK4
- CDK6
- CDK4/6
- CDK4/6 inhibitor
- Phase III
- ER-positive
- PR-positive
- Postmenopausal
