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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02732119
Recruitment Status : Active, not recruiting
First Posted : April 8, 2016
Last Update Posted : January 3, 2019
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Ribociclib Drug: Everolimus Drug: Exemestane Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 14, 2016
Actual Primary Completion Date : October 17, 2018
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: ribociclib + everolimus + exemestane
ribociclib with everolimus and exemestane daily
Drug: Ribociclib
supplied in 50 mg, 200 mg capsules/tablets taken orally and dosed daily for 28 day cycle

Drug: Everolimus
supplied in 2.5 mg tablets taken orally, daily for 28 day cycle

Drug: Exemestane
supplied in 25 mg tablets taken orally, daily for 28 day cycle

Primary Outcome Measures :
  1. Phase I: Maximum Tolerated Dose (MTD) and/or the Recommended Phase II Dose (RP2D) for the triplet combination [ Time Frame: up to 6 months ]
  2. Phase II: Clinical Benefit Rate (CBR) among subjects receiving triplet therapy [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. Phase II: Centrally assessed progression Free Survival (PFS) [ Time Frame: up to approximately 12 months ]
  2. Phase II: Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
    This is defined as the time from treatment initiation with study treatment until death as a result of any cause.

  3. Phase II: Overall Response Rate (ORR) [ Time Frame: Up to approximately 12 months ]
    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

  4. Phase II: Duration of Overall Response (DOR) [ Time Frame: Up to approximately 12 months ]
    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.

  5. Phase II: Time to definitive deterioration of ECOG performance status in one category of the score [ Time Frame: Up to approximately 12 months ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT02732119

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Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals Identifier: NCT02732119     History of Changes
Other Study ID Numbers: CLEE011XUS29
First Posted: April 8, 2016    Key Record Dates
Last Update Posted: January 3, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Advanced breast cancer
CDK4/6 inhibitor
Phase III

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists