Clinical trial NCT02338349: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced ER+, HER2-Negative Breast Cancer
Lead sponsor: Stemline Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-14
Enrollment: 57
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: The first 28 days of treatment.
Secondary outcomes:
measure: Safety and Tolerability of Elacestrant (RAD1901)
timeFrame: Up to 30 days after the end of treatment.
measure: Pharmacokinetics of Elacestrant (RAD1901)
timeFrame: Every 28 days
measure: Anti-Tumor Effect of Elacestrant (RAD1901)
timeFrame: Every 8 weeks
Other outcomes:
Locations:
city: Waltham
country: United States
facility: Radius Pharmaceuticals, Inc.
state: Massachusetts
Study officials:
affiliation: Radius Pharmaceticals, Inc
name: Sr. Director, Clinical Operations
role: STUDY_DIRECTOR
References:
citation: 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.