Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor. (TRINITI-1)

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Breast Cancer

Treatments: Drug: Exemestane; Drug: Everolimus; Drug: Ribociclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02732119

CLEE011XUS29

Details and patient eligibility

About

The purpose of this study is determine if the triplet combination of ribociclib, everolimus and exemastane is safe and effective in the treatment of locally advanced/metastatic breast cancer following treatment with a CDK 4/6 inhibitor

Full description

This trial had two phases. The purpose of Phase I dose escalation and dose de-escalation was to determine the maximum tolerated doses (MTDs) and/or identify the recommended Phase II dose (RP2D) of the combination treatment of ribociclib+ everolimus + exemestane. The dosing was continuous in adult men and postmenopausal women with HR+ HER2-negative advanced breast cancer which was resistant to the non-steroidal aromatase inhibitors, fulvestrant or tamoxifen.

The purpose of the phase II portion of this trial was to evaluate the anti-tumor activity of exemestane, everolimus and ribociclib combination therapy following progression on a CDK 4/6 inhibitor.

The planned duration of the study was 30 months.

Enrollment: 104 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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104 participants in 5 patient groups

Cohort A

Experimental group

Description:

Ribociclib (250 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally for 28 days. If no DLTs occurred, progressed to Cohort B

Treatment:

Drug: Exemestane

Drug: Everolimus

Drug: Ribociclib

Cohort B

Experimental group

Description:

Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally

Treatment:

Drug: Exemestane

Drug: Everolimus

Drug: Ribociclib

Cohort C

Experimental group

Description:

Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally

Treatment:

Drug: Exemestane

Drug: Everolimus

Drug: Ribociclib

Group 1

Experimental group

Description:

Ribociclib (300 mg daily), everolimus (2.5 mg daily) and exemestane (25 mg daily) taken orally

Treatment:

Drug: Exemestane

Drug: Everolimus

Drug: Ribociclib

Group 2

Experimental group

Description:

Ribociclib (200 mg daily), everolimus (5 mg daily) and exemestane (25 mg daily) taken orally

Treatment:

Drug: Exemestane

Drug: Everolimus

Drug: Ribociclib