Breast CancerPhase 2ARIANNANCT04142060

Targeting the PAM50 Her2-Enriched Phenotype With Enzalutamide in Hormone Receptor-Positive/Her2-Negative Metastatic BC

A Phase 2 study testing Enzalutamide in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 8 sites in Spain.

Terminated

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

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Breast Cancer
What is being tested?: Enzalutamide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 8 sitesSpain
Study dates: 1 Jun 2020to 10 Oct 2022
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

Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
Subjects with progression on or following at least 1 prior standard of care systemic anti-cancer therapy.
Female and male patients.
Performance status of 0-2.
Age ≥18 years.
Pre/peri-menopausal and post-menopausal women are allowed; menopausal status is relevant for the requirement of goserelin, triptorelin or leuprolide to be used concomitantly with enzalutamide. Post-menopausal status is defined either by:

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Prior bilateral oophorectomy or
Age ≥60 or
Age < 60 and amenorrhea for ≥ 12 months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the post-menopausal range per local standards.
If a patient is taking tamoxifen or toremifene and is aged < 60, then FSH and plasma estradiol levels should be in post-menopausal range per local values.
For women with therapy-induced amenorrhea, measurement of FSH and/or estradiol are needed to ensure menopausal status.
Life expectancy ≥ 12 weeks.
Locally advanced or metastatic breast cancer not amenable to curative intent.
Histologically confirmed HR-positive/HER2-negative disease based on the most recent biopsy before signing the informed consent.
HER2 negativity is defined as either of the following by local laboratory assessment: IHC 0, IHC 1+ or IHC2+/in situ hybridisation (ISH/FISH) negative as per American Society of Clinical Oncology (ASCO)-College of American Pathologists Guideline (CAP) guideline(73).
ER and/or PR positivity are defined as >1% of cells expressing HR via IHC analysis as per ASCO-CAP guideline (74)
Patients must have a site of disease amenable to safely perform a biopsy, as per Investigator's assessment, and be a candidate for tumor biopsy according to the treating institution's guidelines.
Possibility of performing a biopsy prior to the start of treatment and its repetition after 2 weeks (14-21 days) on the same location. It will be provided formalin-fixed paraffin-embedded (FFPE) tumor block. The tumor tissue should be of good quality based on total and viable tumor content and must be evaluated centrally for PAM50 analysis prior to enrollment. Patients whose tumor tissue is not evaluable for central testing are not eligible. It is recommended to send the biopsy directly to the central lab after confirming the existence of a tumor, so as not to delay the inclusion, without the need to carry out IHC studies in the same.
Acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions or biopsies from bone metastases.
Fine needle aspiration, brushing, cell pellet from pleural effusion and lavage samples are not acceptable.
Patient must be willing to provide biopsy prior to the start of treatment and its repetition after 2 weeks (14-21 days) on the same location.
The following subtypes identified in the pre-treatment tumor biopsy, as assessed by PAM50 assay at the Central Laboratory:
HER2-E (Cohort A)
Luminal A and Luminal B (Cohort B).
No more than 4 prior lines of chemotherapy regimens for recurrent, locally advanced or metastatic breast cancer.
Endocrine resistant disease, defined as the presence of disease recurrence while receiving adjuvant endocrine therapy for early stage breast cancer or disease progression of locally advanced/metastatic BC under ongoing endocrine therapy. There is no limit of previous received hormonal agents.
Measurable and non-measurable (but evaluable) disease per RECIST 1.1 criteria.
Adequate organ function, as determined by the following laboratory tests, within 28 days prior to enrollment:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
Hemoglobin (Hb) ≥ 9 g/dL (red blood cell transfusion and/or erythropoietin allowed 7 days before study treatment).
Platelets ≥ 75,000/mm3.
International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) within therapeutic range
Serum creatinine ≤ 1.5x upper limit of normal (ULN)
AST or ALT ≤ 3 x ULN.
Serum bilirubin ≤ 1.5 upper limit of normal (ULN) unless the patient has documented non-malignant disease (e.g. Gilbert´s syndrome).
Ability to swallow study drug and comply with study requirements.
Resolution of all acute toxic effects of prior therapy or surgical procedures to baseline or Grade ≤ 1 (except alopecia or other toxicities not considered to be a safety risk for the patient) according to NCI CTCAE version 5.0.

Who cannot join

History of current or previously treated CNS metastases or leptomeningeal disease. Testing for CNS metastasis is not mandatory.
History of seizure or any condition that may predispose to seizure.
Clinically significant cardiovascular disease within 6 months prior to enrolment defined as:
Myocardial infarction.
Inadequately controlled angina or serious cardiac arrhythmia not controlled by adequate medication.
Congestive heart failure (CHF) New York Health Association (NYHA) Class ≥ II.

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History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsade de pointes).
History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place.
Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) on 2 consecutive measurements at the screening visit.
Bradycardia as indicated by a heart rate of < 50 beats per minute on the screening electrocardiogram (ECG) recording.
Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the screening visit.
Inability to swallow tablets, extensive reduction surgery of the stomach or small bowel or any active gastrointestinal disorder which may impair the absorption of the trial treatment (e.g. active peptic ulcer disease; uncontrolled celiac disease).
Major surgical procedure within 4 weeks prior to allocation or anticipation of the need for major surgery during the course of study treatment.
Use of medications that could reduce seizure threshold or concomitant treatment with potent CYP3A4 inducers.
Treatment with warfarin and coumarin-like anticoagulants. Prophylactic use of low molecular weight heparin (LMWH) is allowed.
Fructose intolerance.
Treatment with any anticancer commercially available or investigational drug within 14 days prior to commencing trial treatment.
Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.
Current severe disease, infection, or systemic condition that renders the patient inappropriate for enrollment in the opinion of the investigator.
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Has a known history of Human Immunodeficiency Virus (HIV).
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of enzalutamide.
Treatment with any approved or investigational agent that blocks androgen synthesis or targets the AR (eg, abiraterone acetate, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700); or patients who progressed on Exemestane in adjuvant/advanced setting are not allowed; patients who received treatment for < 28 days or placebo on an investigational study are acceptable

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

Spain8 sites

ICO Badalona
Badalona, Barcelona
Hospital Clinic de Barcelona
Barcelona
Hospital Universitari Vall d' Hebrón
Barcelona
Institut Català d'Oncologia Hospitalet
L'Hospitalet de Llobregat, Barcelona
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Fundación de Alcorcón
Madrid
Hospital Universitario Virgen del Rocio
Seville
Fundación Instituto Valenciano de Oncología
Valencia, 46009

Other trials in Spain

About this study

Official title: Targeting the PAM50 Her2-Enriched Phenotype With Enzalutamide in Hormone Receptor-Positive/Her2-Negative Metastatic Breast Cancer

The main hypothesis of the study is that enzalutamide induces a significant proliferative arrest in HR+/HER2-negative breast cancer falling into the PAM50 HER2-E subtype. Currently, enzalutamide clinical development is ongoing in different prostate cancer indications but the breast cancer development program has been discontinued. As the role of the AR in HR-positive breast cancer and the predictive value of previously identified biomarker are still unclear, further research is needed to effectively utilize enzalutamide in this disease.

Read the detailed description

A strong rationale accumulated over the years suggests that within HR+/HER2-negative breast cancer, tumors falling into the PAM50 HER2-enriched subtype have androgen receptor (AR)-dependency. To test this hypothesis directly in patients' tumors, we propose an exploratory, open-label, non-randomized, two-cohort, multicenter, prospective, phase II study which evaluates the effect of enzalutamide on proliferation after 2 weeks (14-21 days) of treatment in patients with endocrine-resistant, locally advanced or metastatic HR+/HER2-negative breast cancer. After 2 weeks (14-21 days) of treatment, patients will continue enzalutamide. Exemestane will be allowed to be added to enzalutamide per investigator discretion and will be administered until progression or unacceptable toxicity.

Conditions: Breast Cancer
Being tested: Enzalutamide
Medical subject headings: Breast Neoplasms

What participants receive

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

EnzalutamideDrug
Also called Xtandi
Patients will be dispensed with oral enzalutamide 160 mg (four 40 mg capsules) as a self-administered single oral daily dose, continuously.

Study groups in NCT04142060
Study group	Role	What they receive
Enzalutamide	Experimental	Patients will be dispensed with oral enzalutamide 160 mg (four 40 mg capsules) as a self-administered single oral daily dose, continuously Receives: Drug: Enzalutamide

What is being measured

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

changes of the PAM50 11-gene proliferation signature
Relative changes of the PAM50 11-gene proliferation signature after 2 weeks (14-21 days) of treatment with enzalutamide. These changes will be analyzed according to the formula: Mean suppression = 100 - [geometric mean (post-treatment / pretreatment · 100)].
Measured: after 2 weeks (14-21 days) of treatment with enzalutamide

Secondary outcomes (8)

Incidence, duration and severity of Adverse Events
Incidence, duration and severity of Adverse Events (AEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5, including dose reductions, delays and treatment discontinuations.
Measured: during and after 2 weeks (14-21 days) of treatment with enzalutamide
Relative changes of 33 gene signatures
Relative changes of 33 gene signatures and 770 genes after 2 weeks (14-21 days) of treatment with enzalutamide and from week 3 to progression (in those patients who consent for optional biopsy). This study will be performed using the nCounter Breast 360TM panel.
Relative changes of 33 gene signatures and 770 genes after 2 weeks (14-21 days) of treatment with enzalutamide and from week 3 to progression (in those patients who consent for optional biopsy). This study will be performed using the nCounter Breast 360TM panel.
Measured: after 2 weeks (14-21 days) of treatment with enzalutamide
somatic mutations
Proportion of somatic mutations in samples from both cohorts using a targeted gene sequencing panel.
Measured: after 2 weeks (14-21 days) of treatment with enzalutamide
AR expression by IHC
Analysis of AR expression by IHC (% nuclear expression in tumoral cell)
Measured: before and after 21 days of treatment in Cohorts A and B.
changes in percentage of cells expressing Ki67 by IHC
Relative changes in percentage of cells expressing Ki67
Measured: after 21 days of enzalutamide in HER2-E and Luminal A/B tumors.
changes of It-TIL and Str-TIL
Analysis of lymphocyte infiltrate on hematoxylin and eosin-stained FFPE-sections. Percentage (%) change in It-TILs and Str-TILs infiltration
Measured: pre- and after 2 weeks (14-21 days) of treatment with enzalutamide and progression
ctDNA levels
Quantification of baseline ctDNA levels and 2 weeks (14-21 days) post-treatment. Determination of quantitative changes at day 21, at progression or at the end of trial due to other reasons
Measured: during and after 2 weeks (14-21 days) of treatment with enzalutamide
tumor ORR
Proportion of patients who have a partial (PR) or complete response (CR) to therapy.
Measured: after 2 weeks (14-21 days) of treatment with enzalutamide

Timeline

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

1 Jun 202010 Oct 2022

First posted29 Oct 2019
Study start1 Jun 2020
Primary completion10 Oct 2022
Study completion10 Oct 2022

Why it stopped: Lack of effectiveness

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Breast CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Model description: an exploratory, open-label, non-randomized, two-cohort, multicenter, prospective, phase II study which evaluates the effect of enzalutamide on proliferation
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04142060
Sponsor's protocol ID: ARIANNA (SOLTI-1502)
Other IDs: 2019-002806-28, 2019
Acronym: ARIANNA
Status last verified: Jun 2022
First submitted: 25 Oct 2019
Last updated: 28 Oct 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Targeting the PAM50 Her2-Enriched Phenotype With Enzalutamide in Hormone Receptor-Positive/Her2-Negative Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT04142060
Acronym / sponsor ID: ARIANNA / ARIANNA (SOLTI-1502)
Conditions: Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Lack of effectiveness
Enrolment: 34 participants (actual)
Lead sponsor: SOLTI Breast Cancer Research GroupUniversity, hospital or other
Study start: 1 Jun 2020 (actual)
Primary completion: 10 Oct 2022 (actual)
Study completion: 10 Oct 2022 (actual)
First posted: 29 Oct 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: an exploratory, open-label, non-randomized, two-cohort, multicenter, prospective, phase II study which evaluates the effect of enzalutamide on proliferation

Arm	Type	Receives
Enzalutamide	Experimental	Drug: EnzalutamidePatients will be dispensed with oral enzalutamide 160 mg (four 40 mg capsules) as a self-administered single oral daily dose, continuously

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (37 listed)

Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
Subjects with progression on or following at least 1 prior standard of care systemic anti-cancer therapy.
Female and male patients.
Performance status of 0-2.
Age ≥18 years.

Key exclusion criteria (25 listed)

History of current or previously treated CNS metastases or leptomeningeal disease. Testing for CNS metastasis is not mandatory.
History of seizure or any condition that may predispose to seizure.
Clinically significant cardiovascular disease within 6 months prior to enrolment defined as:
Inability to swallow tablets, extensive reduction surgery of the stomach or small bowel or any active gastrointestinal disorder which may impair the absorption of the trial treatment (e.g. active peptic ulcer disease; uncontrolled celiac disease).
Major surgical procedure within 4 weeks prior to allocation or anticipation of the need for major surgery during the course of study treatment.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EnzalutamideAlso: XtandiPatients will be dispensed with oral enzalutamide 160 mg (four 40 mg capsules) as a self-administered single oral daily dose, continuously.	Drug	Enzalutamide

Primary outcome

changes of the PAM50 11-gene proliferation signature
Time frame: after 2 weeks (14-21 days) of treatment with enzalutamide
Relative changes of the PAM50 11-gene proliferation signature after 2 weeks (14-21 days) of treatment with enzalutamide. These changes will be analyzed according to the formula: Mean suppression = 100 - [geometric mean (post-treatment / pretreatment · 100)].

8 secondary outcomes

Incidence, duration and severity of Adverse Events
Time frame: during and after 2 weeks (14-21 days) of treatment with enzalutamide
Relative changes of 33 gene signatures
Time frame: after 2 weeks (14-21 days) of treatment with enzalutamide
somatic mutations
Time frame: after 2 weeks (14-21 days) of treatment with enzalutamide
AR expression by IHC
Time frame: before and after 21 days of treatment in Cohorts A and B.
changes in percentage of cells expressing Ki67 by IHC
Time frame: after 21 days of enzalutamide in HER2-E and Luminal A/B tumors.
changes of It-TIL and Str-TIL
Time frame: pre- and after 2 weeks (14-21 days) of treatment with enzalutamide and progression
ctDNA levels
Time frame: during and after 2 weeks (14-21 days) of treatment with enzalutamide
tumor ORR
Time frame: after 2 weeks (14-21 days) of treatment with enzalutamide

Results and safety

The study was stopped early (reason given: Lack of effectiveness). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enzalutamide in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 8 sites in Spain.

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 37 inclusion and 25 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 28 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. 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: Lack of effectiveness). 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?

changes of the PAM50 11-gene proliferation signature (time frame: after 2 weeks (14-21 days) of treatment with enzalutamide). 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 NCT04142060.

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 28 Oct 2022.