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

NCT04142060 | Terminated Phase 2

• 2 other identifiers: ARIANNA (SOLTI-1502)2019-002806-28
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 - \[geometric mean (post-treatment / pretreatment · 100)\].

  after 2 weeks (14-21 days) of treatment with enzalutamide

Secondary Outcomes (8)

• Incidence, duration and severity of Adverse Events

  during and after 2 weeks (14-21 days) of treatment with enzalutamide

• Relative changes of 33 gene signatures

  after 2 weeks (14-21 days) of treatment with enzalutamide

• somatic mutations

  after 2 weeks (14-21 days) of treatment with enzalutamide

• AR expression by IHC

  before and after 21 days of treatment in Cohorts A and B.

• changes in percentage of cells expressing Ki67 by IHC

  after 21 days of enzalutamide in HER2-E and Luminal A/B tumors.

Study Arms (1)

Enzalutamide

EXPERIMENTAL

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

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

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

Also known as: Xtandi

Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead

Study Sites (8)

ICO Badalona

Badalona, Barcelona, Spain

Location

Institut Català d'Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d' Hebrón

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Fundación de Alcorcón

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: an exploratory, open-label, non-randomized, two-cohort, multicenter, prospective, phase II study which evaluates the effect of enzalutamide on proliferation

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: October 29, 2019
• Study Start: June 1, 2020
• Primary Completion: October 10, 2022
• Study Completion: October 10, 2022
• Last Updated: October 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8)