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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Advanced ER+, HER2-Negative Breast Cancer

Intervention / Treatment
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* Drug: Elacestrant


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients must be post-menopausal women, as defined in the protocol 18 years or older Patients with histological or cytological proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced, inoperable and/or metastatic disease Part A, B, C: Patients must have received no more than 2 prior chemotherapeutic regimens and at least 6 months of prior endocrine therapy 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: Prior anticancer or investigational drug treatment within the following windows: Tamoxifen therapy less than 14 days before first dose of study treatment 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 Any other anti-cancer endocrine therapy less than 14 days before first dose of study treatment Any chemotherapy less than 28 days before first dose of study Any investigational drug therapy less than 28 days or 3 half-lives (whichever is longer) prior to first dose of study treatment Patients with untreated or symptomatic central nervous system (CNS) metastases 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elacestrant<br>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 | Drug: Elacestrant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLT) | 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. | The first 28 days of treatment. | 

Secondary Outcome Measures

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