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Trial Title:
Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer
NCT ID:
NCT05816655
Condition:
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Fulvestrant
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fulvestrant plus AI plus ribociclib
Description:
Fulvestrant + AI + ribociclib +/- GnRH agonist
Arm group label:
Fulvestrant arm
Intervention type:
Drug
Intervention name:
AI plus ribociclib
Description:
AI + ribociclib +/- GnRH agonist
Arm group label:
Control arm
Summary:
Aromatase inhibitor (AI) + CDK4/6 inhibitor is settled down as the standard first line
therapy for HR+/HER2- metastatic breast cancer and all three CDk4/6 inhibitors,
palbociclib, ribociclib, and abemaciclib are currently available for same indications.
However, there is no effective treatment strategy for patients who have progressed on
AI+CDK4/6 inhibitor. In particular, the clinical efficacies of subsequent hormone therapy
are lowered when ESR1 mutations, one of mechanisms of AI resistance occur. In the PADA-1
trial, when ESR1 mutations in ctDNA were detected in patients treated with AI+CDK4/6
inhibitor, AI was switched to fulvestrant even if disease progression was not confirmed
clinically. As a result, the median PFS was prolonged by about 8 months in this switching
group compared to the group in which AI was continued. The results of this study
suggested that delaying the occurrence of ESR1 mutations and early response to them are
necessary to increase the effectiveness of hormone therapy.
In SWOG S0226 study, fulvestrant + AI combination showed significant benefits in PFS and
OS compared to AI monotherapy as the first line therapy. Based on these results, the NCCN
guideline suggests fulvestrant + AI combination as one of the first line hormone therapy
options. However, the clinical effect of AI + fulvestrant + CDK4/6 inhibitor has not been
investigated yet. Therefore, the investigators are planning to compare the clinical
efficacy of AI+ fulvestrant + CDK4/6 inhibitor and AI+CDK4/6 inhibitor, and to
investigate if a triple combination regimen can delay the emergence of ESR1 mutations and
modulate occurred ESR1 mutations.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Female ≥ 19 years of age
- Histologically confirmed unresectable, locally advanced or metastatic invasive
breast cancer with hormone receptor positive/HER2 negative
- No previous history of systemic endocrine or chemotherapy for metastatic, advanced
breast cancer.
- If the patient has received AI as adjuvant endocrine therapy, the treatment free
interval (TFI) should be more than 12 months after the end of adjuvant endocrine
therapy. If the patient has received tamoxifen for adjuvant endocrine therapy, TFI
less than 12 months will be allowed.
- ECOG PS 0-2
- Patients should have measurable or evaluable lesion based on RECIST version 1.1
- Patients should have adequate organ function:
- ANC (absolute neutrophil count) ≥ 1.5 × 109/L
- Platelet ≥ 100 × 109/L
- Serum Hb ≥ 9.0 g/dL
- INR ≤1.5
- Serum creatinine ≤ 1.5 X ULN
- ALT & ALT <2.5 X ULN, if patients have hepatic metastasis, ALT & ALT <5.0 X ULN
is allowed
- Total serum bilirubin <1.5 X ULN, if patients have hepatic metastasis, Total
serum bilirubin <3.0 X ULN is allowed.
- In the case of childbearing potential, patients who can adhere to appropriate
contraception during the study period and for at least 6 months after the end of
study treatment.
- Patients who understand the contents of the clinical trial and are cooperative with
the process of the clinical trial.
Exclusion Criteria:
- Patients with a history of previous treatment with a CDK4/6 inhibitor or other
systemic treatment for advanced/metastatic breast cancer
- Patients who have received prior treatment with fulvestrant and any investigational
ER-directed therapy including SERDs (selective estrogen receptor degrader)
- Patients who have disease recurrence on aromatase inhibitor treatment as adjuvant
endocrine therapy
- Patients who have symptomatic or untreated central nervous system metastasis
- Patients who have a history of cardiovascular disease or heart failure as following
conditions; within at least 6 months of myocardial infarction, unstable angina, or
uncontrolled arrhythmia.
- Patients having visceral crisis which needs rapid tumor reduction
- Patients who have a history of any other cancer (except nonmelanoma skin cancer,
carcinoma in-situ of the cervix, well-differentiated thyroid cancer)
- Patients unable to cooperate with periodic blood samples collection
- Patients who have active HBV, HCV infection, immune-suppressive disease, or HIV
infection. In case of chronic HBV infection, HBV DNA should be negative. Patients
with complete remission of HCV infection are allowed.
- Pregnant or breast-feeding women
- Patients who are considered to be unsuitable for this trial by investigators.
Gender:
Female
Minimum age:
19 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Korea university Guro hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
In Hae Park, MD
Phone:
+82-2-2626-3172
Email:
parkih@korea.ac.kr
Facility:
Name:
St Mary Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Jieun Lee, prof
Phone:
+82-2-
Email:
befamiliar@catholic.ac.kr
Start date:
May 31, 2023
Completion date:
June 30, 2029
Lead sponsor:
Agency:
Korea University Guro Hospital
Agency class:
Other
Source:
Korea University Guro Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05816655
