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Phase IB & II Study of Ribociclib With Trastuzumab Plus Letrozole in Postmenopausal HR+, HER2+ Advanced Breast Cancer Patients

NCT03913234 · Status: UNKNOWN · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 95

Last updated 2022-05-10

No results posted yet for this study

Summary

Survival benefit and quality of life are two key elements that should be kept in mind in the treatment of metastatic breast cancer. In this regards, endocrine therapy (ET) is strongly recommended in hormone receptor (HR) positive patients unless there is visceral crisis even though there is no concrete evidence that it is better than chemotherapy in terms of survival.

HER2 positive breast cancer is a subtype of breast cancer that showed the greatest improvement in terms of survival during the last decade due to trastuzumab based therapy. Recently, taxane and HER2 directed doublet including trastuzumab and pertuzumab (THP) is considered as standard of therapy based upon randomized phase 3 clinical trial (CLEOTATRA).

HER2 positive breast cancer can be divided into HER2 enriched subgroup (HR-HER2+) and luminal B subgroup (HR+HER2+) in biologic viewpoint because they are distinctly different subgroups in gene expression analysis. Accordingly, we are currently treating biologically different subtypes in a same way, which is CTx and anti-HER2 combination therapy (THP).

Luminal HER2+ subgroup has actually been tested with endocrine therapy (ET) and anti-HER2 therapy showed better PFS than ET alone (TAnDEM trial and trial comparing lapatinib plus letrozole versus letrozole alone) \[2\],\[3\] confirming existence of cross talk between ER and HER2 pathways in clinical setting. However, the combination regimen between ET and anti-HER2 therapy is not widely used in current practice in ER+HER2+ MBC patients because PFS seemed to be relatively shorter compared with chemotherapy based combination with anti-HER2 therapy even though several guidelines recommend it to be used as an initial treatment unless there is visceral crisis as they recommended ET alone first in ER+HER2- MBC (NCCN 2018).

Recently, various CDK4/6 inhibitors including palbociclib, abemaciclib, and ribociclib were approved by FDA based on the clinical trial results demonstrating prolonged PFS over ET alone when it was combined with ET in ER+ advanced breast cancer \[4\]. In PALOMA 2 biomarker study, it was beneficial regardless of ER and Ki67 expression status.

Reflecting quite durable PFS prolongation (10 month in PALOMA2) shown in ER+ disease (luminal A and luminal B subtype except HR+HER2+ patients) with CDK4/6 inhibitor on top of ET, the hypothesis of this trial is whether CDK4/6 inhibitor could prolong survival in luminal HER2 breast cancer as it did in ER+HER2-patients. In preclinical study, palbociclib showed activity in not only ER+ cell lines but also HER2 positive cell lines \[5\]. Also, in phase Ib trial, a CDK4/6 inhibitor from Lilly, abemaciclib showed acceptable toxicity with endocrine therapy or trastuzumab with response rate of around 20%.

Hence, as of today, it could be justified and warranted to conduct a prospective trial of ribocicib+letrozole+trastuzumab in order to take a look at its efficacy and toxicity in HR+HER2 + advanced breast cancer.

Conditions

Interventions

DRUG

Ribociclib, Trastuzumab, Letrozole

Phase IB: letrozole 2.5mg (fixed dose), trastuzumab (8mg/kg loading followed by 6mg/kg q 3weeks, fixed dose) plus ribociclib (dose escalation from 200mg to 600mg) to identify recommended phase iI dose (RPIID) Phase II: letrozole, trastuzumab (same as phase IB) plus ribocicilb RPIID

Sponsors & Collaborators

  • Yonsei University

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
19 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-06-10
Primary Completion
2023-10-30
Completion
2023-10-30

Countries

  • South Korea

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03913234 on ClinicalTrials.gov