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Hormone Receptor-positive Human Epidermal Growth Factor 2-negativePhase 2NCT06408168

Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial)

A Phase 2 study testing Fulvestrant and Repotrectinib in people with Hormone Receptor-positive Human Epidermal Growth Factor 2-negative and Metastatic Invasive LObular 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

To find out if the combination of repotrectinib and fulvestrant can control the disease in participants with metastatic invasive lobular carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fulvestrant and Repotrectinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
8 Aug 2024to 8 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

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

  • 18 years of age or older.
  • Confirmed ILC with negative E-cadherin immunohistochemistry (IHC) staining on pre-treatment biopsy or archival biopsy.
  • o Participants with ILC who have a germline CDH1 mutation will be included if the E-cadherin IHC staining is negative.
  • Estrogen receptor positive (>1%), progesterone receptor positive or negative, and HER2-negative according to HER2 testing guidelines from the American Society of Clinical Oncology/College of American Pathologists.
  • Patients must be willing to undergo biopsy as required by the study, if the tumor is safely accessible.
  • Participant must have been exposed to a CDK4/6i prior to enrollment.
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  • Participants who received prior chemotherapy, ADCs, mTOR inhibitor and/or PI3K are eligible.
  • o Participants with ESR1 mutation who received prior elacestrant can still enroll on the study. If they did not receive prior fulvestrant they will be enrolled on Cohort 1. If they received prior fulvestrant they will be enrolled on Cohort 2.
  • Participants should not have received more than 2 chemotherapeutic agents and/or ADCs in the metastatic setting.
  • o The enrollment of patients who received 2 or more prior line of therapy (including endocrine therapy) in the metastatic setting will be limited to 50% of the total accrual in both cohorts.
  • Eastern Cooperative Oncology Group (ECOG) Performance status ≤2
  • Participant has either measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1 criteria OR at least one predominantly lytic bone lesion must be present.
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 2 weeks prior to study treatment initiation.
  • WOCBP must agree to use adequate contraception for the duration of study treatment and 7 months after the last dose of study treatment.
  • Participants must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count ≥1,000/mcL Platelets ≥70,000/mcL Total Bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Creatinine ≤ institutional ULN
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Participants with no current symptoms of cardiac disease.
  • Ability to understand and the willingness to sign a written informed consent document.
  • The effects of repotrectinib on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: Postmenopausal (no menses in greater than or equal to 12 consecutive months). History of hysterectomy or bilateral salpingo-oophorectomy. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). History of bilateral tubal ligation or another surgical sterilization procedure.
  • Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Who cannot join

  • Participants with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment.
  • Participants who have had chemotherapy, hormonal therapy, biotherapy, immunotherapy or radiotherapy within 4 weeks prior to entering the study.
  • Systemic small molecule-targeted therapies (eg, tyrosine kinase inhibitors) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug.
  • Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
  • Participants who are receiving any other investigational agents.
  • Participants with prior history of pneumonitis/ILD
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  • Participants with Grade ≥2 ataxia, muscle weakness, dysgeusia, dizziness, paresthesia and/or peripheral neuropathy.
  • Participants with untreated or progressing brain metastases.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to repotrectinib, fulvestrant or other agents used in study.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because repotrectinib and fulvestrant have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with repotrectinib, breastfeeding should be discontinued if the mother is treated with repotrectinib. These potential risks may also apply to other agents used in this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

To find out if the combination of repotrectinib and fulvestrant can control the disease in participants with metastatic invasive lobular carcinoma.

Read the detailed description

Primary Objectives

  • To evaluate the 6-month progression free survival (PFS) of repotrectinib with or without fulvestrant in HR+ HER2- mILC patients who received a prior ET in combination with CDK4/6i

Secondary Objectives

  • To evaluate the 12-month PFS and median PFS (mPFS) of repotrectinib with or without fulvestrant in HR+ HER2- mILC patients who received a prior ET in combination with CDK4/6i
  • To evaluate the overall response rate (ORR) of reporectinib with or without fulvestrant in HR+ HER2- mILC patients who received a prior ET in combination with CDK4/6i
  • To assess the clinical benefit rate (CBR), median duration of response (mDOR), and median overall survival (mOS).
  • To evaluate the safety and tolerability of repotrectinib alone and in combination with fulvestrant, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0

Exploratory/Correlative Objectives

  • To explore response to repotrectinib based on ROS1 and P120 expression by IHC
  • To explore if changes in serum thymidine kinase 1 activity (TKa) between baseline and C1D15 correlates with response
  • To explore whether changes in circulating tumor DNA (ctDNA) levels between baseline and C1D15 predict response to repotrectinib
  • To correlate whole exome sequencing (WES) and RNA sequencing (RNAseq) findings with response (or lack of) to repotrectinib
  • To explore changes in the tumor microenvironment (TME) composition using mIF in response to repotrectinib
Being tested
Fulvestrant, Repotrectinib
Medical subject headings
Carcinoma, Lobular

What participants receive

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

  • FulvestrantDrug

    Also called Faslodex®

    Given by PO

  • RepotrectinibDrug

    Given by IV

Study groups in NCT06408168
Study groupRoleWhat they receive
Cohort 1ExperimentalCohort 1 will include participants who have never received fulvestrant before. The first 15 participants enrolled in Cohort 1 will receive the study drug combination starting on Day 1 of their first treatment cycle. The next 14 participants enrolled in Cohort 1 will begin with fulvestrant alone for at least 12 days and then start repotrectinib sometime between Days 13 and 20 (depending on when their Cycle 1 biopsy is performed). This is done in order to use the biopsy results to study the effects of fulvestrant alone in these patients.
Receives: Drug: Fulvestrant; Drug: Repotrectinib
Cohort 2ExperimentalAbout 6 months after the first 15 participants are enrolled, based on their study data, Cohort 2 will begin enrolling up to 29 participants who have received fulvestrant in earlier treatments. Participants in Cohort 2 will receive repotrectinib alone.
Receives: Drug: Repotrectinib

What is being measured

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

  1. Safety and adverse events (AEs)

    Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    Measured: Through study completion; an average of 1 year

Timeline

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

  1. First posted10 May 2024
  2. Study start8 Aug 2024
  3. Primary completion8 Dec 2025
  4. Study completion8 Dec 2025

Why it stopped: \<75% Participation

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06408168
Sponsor's protocol ID
2024-0099
Other IDs
NCI-2024-03805
Status last verified
Dec 2025
First submitted
30 Apr 2024
Last updated
5 Jan 2026
Results posted
No
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 Fulvestrant and Repotrectinib in people with Hormone Receptor-positive Human Epidermal Growth Factor 2-negative and Metastatic Invasive LObular 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 24 inclusion and 11 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 5 Jan 2026. 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?

The study was stopped early (reason given: \<75% Participation). Results are not available in the source record.

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?

Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06408168.

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 5 Jan 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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