Phase IB Study to Evaluate RAD1901 on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Cancer

A Phase IB Study to Evaluate the Effect of RAD1901 on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Cancer Lesions Using 16α-18F-Fluoro-17β-Estradiol Positron Emission Tomography Imaging

The purpose of this study is to visualize and quantify ER-binding sites during treatment with Elacestrant (RAD1901)

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: RAD1901

Detailed Description

The purpose of this study is to visualize and quantify ER-binding sites during treatment with Elacestrant (RAD1901) using 16α-18F-Fluoro-17β-estradiol (FES) positron emission tomography (PET) imaging

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet
  • Leuven, Belgium, 3000
    • Uz Leuven Campus Gasthuisberg
• Netherlands
  • Amsterdam, Netherlands
    • Vrije Universiteit Medisch Centrum (Vumc)
  • Groningen, Netherlands
    • Universitair Medisch Centrum Groningen (UMCG)
  • Rotterdam, Netherlands
    • Erasmus Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Key Inclusion Criteria:

1. Patients with histologically-proven, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced, inoperative, and/or mBC
2. Tumor progression after ≥ 6 months of at least 1 line of hormonal systemic treatment (SERM, SERD, or aromatase inhibitor) in the metastatic setting
3. Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1 or clinically evaluable disease
4. Greater than or equal to 18 years of age
5. Patients must be post-menopausal
6. Life expectancy >3 months

Key Exclusion Criteria:

1. Greater than 3 lines of endocrine therapy for metastatic disease.

2. Prior anti-cancer treatment or investigational drug therapy within the following windows:

   1. Tamoxifen or fulvestrant therapy < 42 days before 1st 18FES-PET scan
   2. Any other anti-cancer endocrine therapy < 14 days before 1st dose of study drug
   3. Any chemotherapy < 28 days before 1st dose of study drug
   4. Any investigational drug therapy < 28 days or 3 half-lives (whichever is longer) prior to the 1st dose of study drug 2. Patients with untreated or symptomatic central nervous system (brain) metastases 3. Patients with known endometrial disorders, including evidence of endometrial hyperplasia, dysfunctional uterine bleeding, or cysts

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elacestrant (formerly RAD1901); To receive daily oral elacestrant	Drug: RAD1901; RAD1901, a novel selective ER degrader (SERD); Other Names: Elacestrant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of ER Binding after RAD1901 treatment	To determine the effect of RAD1901 treatment on the estrogen receptor (ER) expression and estradiol binding to the ER in lesions from patients with metastatic breast cancer (mBC)	14 Days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of FES uptake after RAD1901 treatment to clinical response	To determine if any changes in ER binding, as observed through FES uptake, correlate with clinical response	Every 8 weeks for to up 12 months of treatment
Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines	To determine if there is a tumor response to RAD1901 treatment	Every 8 weeks for to up 12 months of treatment
Safety and Tolerability assessed in terms of adverse events, serious adverse events, ECG, physical examination, ECOG performance status, vital signs, and laboratory values	Characterization of the safety of RAD1901 in this patient population	Up to 30 days after the end of treatment
Plasma concentrations of RAD1901 will be assessed at predefined intervals	Pharmacokinetic data will be collected.	Every 28 days for up to 3 cycles

Collaborators and Investigators

• Sponsor: Stemline Therapeutics, Inc.
• Investigators: Principal Investigator: Elisabeth GE de Vries, MD, Universitair Medisch Centrum Groningen (UMCG)

Publications and helpful links

General Publications

• Jager A, de Vries EGE, der Houven van Oordt CWM, Neven P, Venema CM, Glaudemans AWJM, Wang Y, Bagley RG, Conlan MG, Aftimos P. A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging. Breast Cancer Res. 2020 Sep 11;22(1):97. doi: 10.1186/s13058-020-01333-3.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): August 30, 2018
• Study Completion (Actual): October 18, 2019

Study Registration Dates

• First Submitted: January 6, 2016
• First Submitted That Met QC Criteria: January 7, 2016
• First Posted (Estimate): January 8, 2016

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: RAD1901-106; 2015-003555-22 (EudraCT Number); L54809.042.15 (Other Identifier: ABR nr)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No