MedDataX Logo

Aromatase Inhibitor Therapy With or Without Fulvestrant for the Treatment of HR Positive Metastatic Breast Cancer With an ERS1 Activating Mutation, the INTERACT Study

NCT ID: NCT04256941

Last Updated: 2024-12-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-31

Study Completion Date

2023-09-22

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase II trial studies how well letrozole, anastrozole, or fulvestrant work when given together with ribociclib, palbociclib, and/or abemaciclib in treating patients with hormone receptor (HR) positive breast cancer that has spread to other places in the body (metastatic) and has an ERS1 activating mutation. Letrozole, anastrozole, ribociclib, palbociclib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known if giving letrozole, anastrozole, or fulvestrant with ribociclib, palbociclib, and/or abemaciclib will work better in treating patients with breast cancer.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVE:

I. To assess progression free survival (PFS) with transition to fulvestrant compared with continuing aromatase inhibitor (AI) therapy in patients with emergence of estrogen receptor 1 (ESR1) mutations in plasma.

SECONDARY OBJECTIVES:

I. To assess circulating tumor deoxyribonucleic acid (ctDNA) ESR1 mutant allele fraction (MAF) and kinetics with fulvestrant compared with AI.

II. To assess the prevalence of ESR1 mutations in patients with secondary resistance to endocrine therapy.

III. To correlate ctDNA with cancer antigens (CA) 15-3 tumor marker changes. IV. To assess overall survival (OS) with transition to fulvestrant compared with continuing AI therapy in patients with emergence of ESR1 mutations.

V. To assess PFS and time to next treatment (TTNT) on next line of therapy after progression on fulvestrant versus (vs.) AI in combination with CDKI.

EXPLORATORY OBJECTIVES:

I. Characterize other co-existing actionable genomic alterations of interest in relation to ESR1 and clinical outcomes.

II. To determine frequency of other actionable genomic alterations and frequency of enrollment on genotype-matched therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ribociclib orally (PO) once daily (QD), palbociclib PO QD on days 1-21, and/or abemaciclib PO twice daily (BID) on days 1-28. Patients also receive fulvestrant intramuscularly (IM) for 2 injections over 1-2 minutes each on days 1 and 15 of cycle 1 and day 2 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ribociclib orally PO QD, palbociclib PO QD on days 1-21, and/or abemaciclib PO BID on days 1-28. Patients also receive letrozole PO QD or anastrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Anatomic Stage IV Breast Cancer AJCC v8 Metastatic Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant)

Patients receive ribociclib PO QD, palbociclib PO QD on days 1-21, and/or abemaciclib PO BID on days 1-28. Patients also receive fulvestrant IM for 2 injections over 1-2 minutes each on days 1 and 15 of cycle 1 and day 2 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Abemaciclib

Intervention Type DRUG

Given PO

Fulvestrant

Intervention Type DRUG

Given IM

Palbociclib

Intervention Type DRUG

Given PO

Ribociclib

Intervention Type DRUG

Given PO

Arm II (ribociclib, palbociclib, abemaciclib, letrozole)

Patients receive ribociclib orally PO QD, palbociclib PO QD on days 1-21, and/or abemaciclib PO BID on days 1-28. Patients also receive letrozole PO QD or anastrozole PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type ACTIVE_COMPARATOR

Abemaciclib

Intervention Type DRUG

Given PO

Anastrozole

Intervention Type DRUG

Given PO

Letrozole

Intervention Type DRUG

Given PO

Palbociclib

Intervention Type DRUG

Given PO

Ribociclib

Intervention Type DRUG

Given PO

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Abemaciclib

Given PO

Intervention Type DRUG

Anastrozole

Given PO

Intervention Type DRUG

Fulvestrant

Given IM

Intervention Type DRUG

Letrozole

Given PO

Intervention Type DRUG

Palbociclib

Given PO

Intervention Type DRUG

Ribociclib

Given PO

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

LY-2835219 LY2835219 Verzenio Anastrazole Arimidex ICI D1033 ICI-D1033 ZD-1033 Faslodex Faslodex(ICI 182,780) ICI 182,780 ICI 182780 ZD9238 CGS 20267 Femara 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one Ibrance PD 0332991 PD 332991 PD 991 PD-0332991 Kisqali LEE-011 LEE011

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelets \>= 50 x 10\^9/L
* Hemoglobin (Hb) \>= 9 g/dL
* Total serum bilirubin =\< 2.0 mg/dL
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN) (=\< 5 x ULN in patients with liver metastases)
* Serum creatinine =\< 1.5 x ULN
* Activating ESR1 mutation (e.g. D538G, Y537S/N, S463P) identified on ctDNA. Novel ESR1 alterations allowed as per discretion of principal investigator (PI)
* On AI with CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) as first line therapy for metastatic breast cancer (MBC) for at least 12 months without evidence of clinical progression
* Patients with histologically confirmed HR positive (estrogen receptor \[ER\] positive \[+\] and/or progesterone receptor \[PR\]+ \[\> 10%\]), MBC

Exclusion Criteria

* Pregnant or lactating women
* Received prior therapy for MBC (except for AI use for up to 4 weeks prior to initiation of CDK4/6 inhibitor)
* Prior therapy with fulvestrant in the metastatic setting
* Corrected QT (QTc) interval \> 480 msec, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes
* Psychiatric illness which would limit informed consent
* Patients with de novo metastatic disease
* Patients who have any severe and/or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =\< 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease, active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable hepatitis B virus \[HBV\]-DNA and/or positive hepatitis B surface antigen \[HbsAg\], quantifiable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\]), severe hepatic impairment (Child-Pugh C)
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
* Expected survival \< 6 months
* Any serious medical illness, other than that treated by this study, which would limit survival to less than 1 month
* Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
* Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
* Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after the end of treatment. Highly effective contraception methods include combination of any two of the following: placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; total abstinence or; male/female sterilization
* Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Senthilkumar Damodaran, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2019-08825

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-0287

Identifier Type: OTHER

Identifier Source: secondary_id

2018-0287

Identifier Type: -

Identifier Source: org_study_id