AzTrials
AzTrials

ER-positive Breast CancerPhase 2NCT04738292

Onapristone and Fulvestrant for ER+ HER2- Metastatic Breast Cancer After Endocrine Therapy and CDK4/6 Inhibitors (The SMILE Study)

A Phase 2 study testing Onapristone and Fulvestrant in people with ER-positive Breast Cancer and HER2-negative Breast Cancer, run by University of Wisconsin, Madison at 2 sites in United States.

Terminated

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

Official record
Search all trials

Trial summary

A phase II single-arm trial of onapristone in combination with fulvestrant for women and men with ER-positive, PgR-positive or negative and HER2-negative locally advanced or metastatic breast cancer after progression on aromatase and CDK4/6 inhibitors. The study will enroll up to 39 participants. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Onapristone and Fulvestrant
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
2 sitesUnited States
Study dates
5 Oct 2021to 15 May 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

  • Advanced ER+, (PgR positive or negative), and HER2 negative breast cancer. Advanced is defined as locally advanced or locoregionally recurrent or metastatic and not amenable to curative therapy.
  • Below-mentioned prior lines of therapy are allowed in the adjuvant and or metastatic ER+/HER2- setting.
  • Participants must have had prior endocrine therapy either in the adjuvant or metastatic setting (SERM (tamoxifen, raloxifene, toremifene) or any of the aromatase inhibitors (anastrozole, letrozole, exemestane), or oral selective estrogen receptor degrader (SERD) on a clinical trial either in the adjuvant or metastatic setting
  • Participants must have received prior therapy with oral cyclin-dependent kinase (CDK)4/6 inhibitors in the metastatic setting
  • Other standard therapies in the metastatic setting (such as mTOR inhibitors) are allowed
  • Patients who previously received any one of the standard adjuvant chemotherapy regimens in a curative setting are eligible for this study.
Show all 27Show fewer
  • One line of prior chemotherapy in the metastatic setting is allowed (i.e. any single agent or doublet cytotoxic chemotherapy, not limited to xeloda).
  • Histologically and/or cytologically confirmed diagnosis of ER+, PgR+/- and HER2- breast cancer by local laboratory at diagnosis of metastatic disease. Hormone receptor positivity is defined as ER and PgR positivity in at least 1% cells by immunohistochemistry (IHC). HER2-negative breast cancer is defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization test is required.
  • Measurable disease, i.e., at least one measurable lesion, as per RECIST 1.1 criteria. A palpable, and measurable breast mass is acceptable.
  • Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2
  • Adequate organ function as defined by
  • aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 times institutional upper limit.
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN), except for subjects with Gilbert's syndrome who may be included if their total bilirubin is ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN.
  • Alkaline phosphatase (ALP) ≤ 2.5 times institutional upper limit with exception that ALP of < 5 x ULN is acceptable in patients with elevated with ALP due to bone metastases (in the absence of liver metastases).
  • Serum creatinine <1.5 × ULN.
  • Absolute neutrophil count (ANC) ≥1000/µL.
  • Participants with lymphopenia are eligible at the discretion of the treating provider
  • Hemoglobin (Hb) ≥ 8g/dL.
  • Platelet count ≥ 100,000/µL
  • Female participants must meet one of the following:
  • Postmenopausal for at least one year before enrollment, or
  • Surgically sterile (i.e., undergone bilateral oophorectomy), or
  • Premenopausal is defined as someone who has had menses at any time in the preceding 12 months. Premenopausal women who are eligible for this trial will require a Gonadotropin-releasing hormone (GnRH) analogue and treating physician may choose to monitor the ovarian function with laboratory tests to ensure a complete menopausal status with cessation of menses
  • Women of childbearing potential must have a negative pregnancy test within seven days of registration. Participants must have a negative pregnancy test seven to 10 days prior to starting study treatment
  • A formalin fixed paraffin embedded (FFPE) tumor biopsy block or up to 20 superplus frost slides with unstained histological sections at 4 micrometer thickness are required at the time of study entry. Archived tumor tissue acceptable (metastatic disease from non-bone and non-brain sites preferred, but primary breast or lymph node tissue is permitted) if obtained in the 18 months prior to study registration, otherwise a fresh biopsy will be required if deemed safe by the treating physician (minimal risk to patient). Confirmation of adequate and available tissue sample is to be determined by the site's pathologist. Tumor samples do not need to be shipped for eligibility purposes. Tumor samples do not need to be shipped until subject is confirmed eligible and is registered for treatment.
  • Ability to take oral medications (without crushing). Please refer to section 6.1.2 for directions on taking the study drug (onapristone).
  • To participate in the optional 18F-FFNP PET/CT imaging, the subject must have ER positive, HER2 negative, AND PgR positive disease and at least one extra hepatic lesion measuring at least 10 mm in size.

Who cannot join

  • Prior treatment with an anti-progesterone agent.
  • Prior treatment with fulvestrant in the metastatic setting
  • Prior treatment with CDK4/6 inhibitors in the neoadjuvant/adjuvant setting
  • History of malignancy other than breast cancer within three years prior to registration except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ.
  • History or presence of clinically active, and symptomatic central nervous system (CNS) metastasis: If the patient fulfills the following criteria, they will be eligible for the trial:
  • Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of study treatment and CNS tumor is clinically stable at the time of screening and patient is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases.
Show all 20Show fewer
  • Participants with any of the following conditions:
  • Clinically significant illness or systemic disease as determined by the treating physicians.
  • Active hepatitis or uncontrolled infection or any other clinically significant cirrhosis or other disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. Testing for infectious hepatitis is not required for the study. Treating provider may choose additional testing if indicated clinically.
  • Patients who have had systemic chemotherapy, or targeted therapy, within two weeks prior to starting study treatment or those who have not recovered from acute effects of any prior therapy to baseline or Grade ≤1. Grade 2 or higher exceptions include alopecia, up to grade 2 neuropathy or other grade 2 adverse events (AEs) or lab values not constituting a safety risk in the pinion of the treating physician. NCI CTCAE v5.0 will be used.
  • Co-administration with any prescriptions during the four weeks prior to first onapristone dosing and concerns for possible drug interactions should be discussed with the pharmacist
  • Patients who are pregnant or breast feeding
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to registration..
  • Symptomatic congestive heart failure (New York Heart Association III-IV)
  • Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular block (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block).
  • Any episode of atrial fibrillation in the prior 12 months.
  • QT interval >480 msec.
  • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome.
  • Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication.
  • Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53705

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: A Phase II Trial of OnapriStone in CoMbInation With FuLvestrant for Patients With ER-positive, and HER2-negative Metastatic Breast Cancer After Progression on Endocrine Therapy and CDK 4/6 Inhibitors

A phase II single-arm trial of onapristone in combination with fulvestrant for women and men with ER-positive, PgR-positive or negative and HER2-negative locally advanced or metastatic breast cancer after progression on aromatase and CDK4/6 inhibitors. The study will enroll up to 39 participants.

Being tested
Onapristone, Fulvestrant
Medical subject headings
Neoplasm Metastasis

What participants receive

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

  • OnapristoneDrug

    Onapristone is a type I antiprogestin which prevents the PgR from dimerizing and blocks ligand induced protein kinase-mediated phosphorylation of the PgR.

  • FulvestrantDrug

    Also called Fulvestrant Injection

    Fulvestrant binds, blocks and degrades the ER, completely inhibiting ER signaling.

Study groups in NCT04738292
Study groupRoleWhat they receive
Onapristone In Combination with FulvestrantExperimentalAll participants will receive onapristone 50 mg p.o. BID (twice) daily and fulvestrant (500 mg) intramuscular injection on days 1, 15 (cycle 1), then two weeks later (cycle 2, day1), then once every 28 days thereafter. A cycle is defined as 28 days. There will be no breaks between dosing cycles.
Receives: Drug: Onapristone; Drug: Fulvestrant

What is being measured

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

  1. Number of Participants With Objective Response (ORR)

    Best overall response of complete response (CR) or partial response (PR), as per RECIST 1.1. Point and 95% interval estimate of ORR will be evaluated accounting for possibility of early futility stopping.

    Measured: up to 17 months

Secondary outcomes (5)

  1. Number of Participants Experiencing Progression Free Survival (PFS)

    Time from date of enrollment to the date of first documented disease progression or death due to any cause. PFS will be described with Kaplan-Meier (KM) Curve and its pointwise asymptotic 95% confidence bounds. Median PFS if reached will be extracted from this KM estimator.

    Measured: up to 17 months

  2. Number of Participants With Disease Control (DCR)

    Best overall response of CR, PR or stable disease (SD) lasting for ≥ 24 weeks, as per RECIST 1.1. DCR will be estimated with relative frequency and exact two-sided 95% binomial confidence interval.

    Measured: up to 17 months

  3. Time to Response

    Time from registration to first documented response (CR or PR) will be evaluated with a cumulative incidence where death will be as a competing risk to response.

    Measured: up to 17 months

  4. Duration of Response

    Time between the first date of documented response to progression or death due to breast cancer. Duration of response will be assessed for a subgroup of subjects with observed response. The date of response will be denoted as time zero and time to progression or death will be evaluated with KM curve and 95% confidence interval (CI). Median time to response will be extracted from this KM curve.

    Measured: up to 17 months

  5. Incidence of Treatment-Related Adverse Events

    Type, frequency and severity of adverse events and laboratory abnormalities (according to CTCAE version 5.0) will be summarized with descriptive frequency tables. See Adverse Events Section for detailed summary.

    Measured: up to 17 months

Timeline

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

  1. First posted4 Feb 2021
  2. Study start5 Oct 2021
  3. Primary completion3 Apr 2023
  4. Study completion15 May 2023

Why it stopped: funding

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04738292
Sponsor's protocol ID
UW20037
Other IDs
A534260, SMPH/MEDICINE/HEM-ONC, 2020-0877, NCI-2021-00371, Protocol Version 8/26/2021
Status last verified
May 2024
First submitted
1 Feb 2021
Last updated
3 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Onapristone and Fulvestrant in people with ER-positive Breast Cancer and HER2-negative Breast Cancer, run by University of Wisconsin, Madison at 2 sites 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 27 inclusion and 20 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 3 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 3 May 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?

Number of Participants With Objective Response (ORR) (time frame: up to 17 months). 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 NCT04738292.

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 3 May 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in