A Phase I, Multicenter, Open-Label, Multi-Part, Dose-escalation Study of RAD1901 in Postmenopausal Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer

• ClinicalTrials.gov Identifier: NCT02338349
• Recruitment Status: Completed
• First Posted: January 14, 2015
• Last Update Posted: August 18, 2022
• Sponsor: Stemline Therapeutics, Inc.
• Information provided by (Responsible Party): Stemline Therapeutics, Inc.

Tracking Information

• First Submitted Date: December 31, 2014
• First Posted Date: January 14, 2015
• Last Update Posted Date: August 18, 2022
• Actual Study Start Date: January 2015
• Actual Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2018)

Dose Limiting Toxicities (DLT) [ Time Frame: The first 28 days of treatment. ]

To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of Elacestrant (RAD1901), the incidence of Dose Limiting toxicities (DLTs) will be assessed.

Original Primary Outcome Measures (submitted: January 13, 2015)

Dose Limiting Toxicities (DLT) [ Time Frame: The first 28 days of treatment. ]

To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of RAD1901, the incidence of Dose Limiting toxicities (DLTs) will be assessed during the first 28 days.

Current Secondary Outcome Measures (submitted: January 19, 2018)

• Safety and Tolerability of Elacestrant (RAD1901) [ Time Frame: Up to 30 days after the end of treatment. ]
  Safety and tolerability will be assessed in terms of adverse events, serious adverse events, ECG, physical examination, vital signs, and laboratory values.
• Pharmacokinetics of Elacestrant (RAD1901) [ Time Frame: Every 28 days ]
  Plasma concentrations of RAD1901 will be assessed at predefined intervals
• Anti-Tumor Effect of Elacestrant (RAD1901) [ Time Frame: Every 8 weeks ]
  Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines.

Original Secondary Outcome Measures (submitted: January 13, 2015)

Safety and Tolerability assessed in terms of adverse events, serious adverse events, ECG, physical examination, vital signs, and laboratory values [ Time Frame: Up to 30 days after the end of treatment. ]

Safety and tolerability will be assessed in terms of adverse events, serious adverse events, ECG, physical examination, vital signs, and laboratory values.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: January 13, 2015)

• Plasma concentrations of RAD1901 will be assessed at predefined intervals. [ Time Frame: Every 28 days for up to 12 months of treatment. ]
• Tumor response will be evaluated in patients with measurable or evaluable disease, using RECISTv1.1 guidelines. [ Time Frame: Every 8 weeks until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months of treatment. ]

Descriptive Information

• Brief Title: A Phase I, Multicenter, Open-Label, Multi-Part, Dose-escalation Study of RAD1901 in Postmenopausal Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer
• Official Title: A Phase I, Multicenter, Open-Label, Multi-Part, Dose-escalation Study of RAD1901 in Postmenopausal Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer
• Brief Summary: The purpose of this study is to evaluate the safety, tolerability and preliminary efficacy of elacestrant (RAD1901) in patients with advanced ER+, HER2-negative breast cancer.

Detailed Description

The primary objective is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of elacestrant in patients with advanced ER+HER2-negative breast cancer.

The secondary objectives of this study are:

• To assess the safety and tolerability of elacestrant
• To evaluate the pharmacokinetics (PK) of elacestrant
• To evaluate the preliminary anti-tumor effect of elacestrant

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced ER+, HER2-Negative Breast Cancer
• Intervention: Drug: Elacestrant

Study Arms

Experimental: Elacestrant

Part A, Dose Escalation: Patients will be assigned sequentially to escalating doses of elacestrant.

Part B, Safety Expansion: Once the MTD has been identified and/or a RP2D has been selected, additional patients will be enrolled to further evaluate the safety, tolerability and preliminary efficacy of the RP2D.

Part C, Tablet Introduction: A cohort of patients will be enrolled to evaluate the safety, tolerability, and PK of a tablet dosage form at 400 mg QD.

Part D, Dose Expansion: A cohort of patients will be enrolled to evaluate the safety, tolerability, PK and preliminary anti-tumor effect of elacestrant in tablet dosage form at 400 mg QD PO in a group of patients with a more homogeneous prior treatment history

Intervention: Drug: Elacestrant

• Publications *: Bardia A, Kaklamani V, Wilks S, Weise A, Richards D, Harb W, Osborne C, Wesolowski R, Karuturi M, Conkling P, Bagley RG, Wang Y, Conlan MG, Kabos P. Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer. J Clin Oncol. 2021 Apr 20;39(12):1360-1370. doi: 10.1200/JCO.20.02272. Epub 2021 Jan 29.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 30, 2018): 57
• Original Estimated Enrollment (submitted: January 13, 2015): 38
• Actual Study Completion Date: April 2020
• Actual Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Patients must be post-menopausal women, as defined in the protocol
2. 18 years or older
3. Patients with histological or cytological proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced, inoperable and/or metastatic disease
4. Part A, B, C: Patients must have received no more than 2 prior chemotherapeutic regimens and at least 6 months of prior endocrine therapy
5. Part D: Patients may have received up to 1 previous line of chemotherapy and must have previously received 2 or more lines of endocrine therapy for advanced/metastatic breast cancer as a single agent or in combination. Patients must have received fulvestrant as one of the previous lines of endocrine therapy and have had documented progression while on, or within 1 month after the end of, fulvestrant therapy for advanced/metastatic breast cancer. Patients must have received prior treatment with a CDK4/6 inhibitor

Note: This list is not complete. Further inclusion criteria is provided in the protocol synopsis.

Key Exclusion Criteria:

1. Prior anticancer or investigational drug treatment within the following windows:

   1. Tamoxifen therapy less than 14 days before first dose of study treatment
   2. Part A, B and C: Fulvestrant therapy less than 90 days before first dose of study treatment. Part D: Fulvestrant therapy less than 42 days before first dose of study treatment
   3. Any other anti-cancer endocrine therapy less than 14 days before first dose of study treatment
   4. Any chemotherapy less than 28 days before first dose of study
   5. Any investigational drug therapy less than 28 days or 3 half-lives (whichever is longer) prior to first dose of study treatment
2. Patients with untreated or symptomatic central nervous system (CNS) metastases
3. Patients with endometrial disorders, including evidence of endometrial hyperplasia, dysfunctional uterine bleeding or cysts

Note: This list is not complete. Further exclusion criteria is provided in the protocol synopsis.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02338349
• Other Study ID Numbers: RAD1901-005
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Stemline Therapeutics, Inc.
• Original Responsible Party: Radius Health, Inc.
• Current Study Sponsor: Stemline Therapeutics, Inc.
• Original Study Sponsor: Radius Health, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Sr. Director, Clinical Operations; Radius Pharmaceticals, Inc

• PRS Account: Stemline Therapeutics, Inc.
• Verification Date: May 2020