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Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT04256941

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

A Phase 2 study testing Abemaciclib, Anastrozole and Fulvestrant in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Abemaciclib, Anastrozole and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
31 May 2019to 22 Sep 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: INTERACT- Integrated Evaluation of Resistance and Actionability Using Circulating Tumor DNA in HR Positive Metastatic Breast Cancers

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbemaciclibDrug

    Also called LY-2835219, LY2835219, Verzenio

    Given PO

  • AnastrozoleDrug

    Also called Anastrazole, Arimidex, ICI D1033, ICI-D1033

    Given PO

  • FulvestrantDrug

    Also called Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780

    Given IM

  • LetrozoleDrug

    Also called CGS 20267, Femara

    Given PO

  • PalbociclibDrug

    Also called 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

    Given PO

  • RibociclibDrug

    Also called Kisqali, LEE-011, LEE011

    Given PO

Study groups in NCT04256941
Study groupRoleWhat they receive
Arm I (ribociclib, palbociclib, abemaciclib, fulvestrant)ExperimentalPatients 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.
Receives: Drug: Abemaciclib; Drug: Fulvestrant; Drug: Palbociclib; Drug: Ribociclib
Arm II (ribociclib, palbociclib, abemaciclib, letrozole)Active comparatorPatients 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.
Receives: Drug: Abemaciclib; Drug: Anastrozole; Drug: Letrozole; Drug: Palbociclib; Drug: Ribociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    Survival curves for PFS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.

    Measured: Up to 30 days

Secondary outcomes (5)
  1. Circulating Tumor Deoxyribonucleic Acid (ctDNA) ESR1 Mutant Allele Fraction (MAF) and Kinetics

    Graphical analysis, such as scatter plots with Lowess smoothers, will be used to assess the correlative structure of outcomes and compare MAF between fulvestrant and aromatase inhibitor-treated groups. The Pearson correlation, or its non-parametric analogue, the Spearman correlation, will be used to estimate the linear correlation among variables.

    Measured: Up to 30 days

  2. Prevalence of Emergence of Estrogen Receptor 1 (ESR1) Mutations

    Will be assessed by the secondary resistance of endocrine therapy.

    Measured: Up to 30 days

  3. Changes in Cancer Antigens (CA) 15-3 Tumor Marker

    Will correlate ctDNA with CA 15-3 tumor marker changes.

    Measured: Up to 30 days

  4. Overall Survival (OS)

    Survival curves for OS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.

    Measured: Up to 30 days

  5. Time to Next Treatment

    Will be assessed on next line of therapy after progression.

    Measured: Up to 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2020
  2. Study start31 May 2019
  3. Primary completion22 Sep 2023
  4. Study completion22 Sep 2023

Why it stopped: Despite modifications, accrual was poor and the closed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04256941
Sponsor's protocol ID
2018-0287
Other IDs
NCI-2019-08825, 2018-0287
Status last verified
Dec 2024
First submitted
21 Jan 2020
Last updated
27 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Abemaciclib, Anastrozole and Fulvestrant in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: Up to 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.

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