Summary of Study ST003315

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002062. The data can be accessed directly via it's Project DOI: 10.21228/M82Z4P This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST003315
Study Title	Randomized phase II trial of pre-operative fulvestrant with or without enzalutamide for ER+/Her2- primary breast cancer: effects on tumor immune microenvironment and clinical outcomes.
Study Summary	This randomized phase II trial of 4 months of neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) assessed whether the addition of AR blockade to Fulv would limit residual tumor at time of surgery, as measured by modified preoperative endocrine predictive index (PEPI) score. Eligible patients were women with ER+/HER2- primary BC cT2 or greater. Lithium-heparin (LiHep) plasma samples were obtained every 4 weeks until surgery and one month after surgery then analyzed by MS-based metabolomics.
Institute	University of Colorado Anschutz Medical Campus
Last Name	Haines
First Name	Julie
Address	12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA
Email	julie.haines@cuanschutz.edu
Phone	3037243339
Submit Date	2024-06-28
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2024-08-01
Release Version	1

Select appropriate tab below to view additional metadata details:

Treatment:

Treatment ID:	TR003445
Treatment Summary:	Study design and treatments NCT02955394 (COMIRB 16-1042) was an open-label randomized phase II trial of fulvestrant with or without enzalutamide. Fulvestrant 500 mg IM was administered on day 1, 15, 29, and then every 4 weeks for a total of 4 months. Enzalutamide 160 mg po daily was given concurrently for 4 months for those women assigned to the combination (Fig. 1A). Surgery was anticipated to occur immediately after week 17, upon completion of enzalutamide; however timing was subject to surgeon and operating suite availability. As drug supply was limited, enzalutamide could not always be continued until the day prior to surgery as originally planned. Stratification factors were institution, clinical node status (N0,N+), and T-stage (T2,T3/4). Pre- or peri-menopausal women received concurrent ovarian suppression with a gonadotropinreleasing hormone agonist. The study was conducted at the Universities of Colorado and Tennessee and Memorial Sloan Kettering Cancer Center. The study protocol and its amendments 16 were approved by the respective Institutional Review Boards as well as the Department of Defence HRPO committee. All patients provided written informed consent prior to participating in the study. The study was conducted under the principles of the World Medical Association, Declaration of Helsinki, and Good Clinical Practice guidelines of the International Conference on Harmonisation. The study did not require an Investigational New Drug Application. Drug support (enzalutamide) was provided by Astellas and Pfizer as part of this investigator-sponsored research study. Study population Eligible patients were women ≥18 years of age with adequate organ and bone marrow function and an ECOG performance score (PS) of 2 or less. All had primary breast cancer of at least 2 cm in size (>T2, N0-2, M0) determined to be ER positive and HER2 negative. Men were excluded due to potential confounding from androgenic stimuli. History of seizures was exclusionary due to the toxicity profile of enzalutamide. Determination of AR expression was not a requirement as it was expected that ~90% of tumors would stain for AR, and the assay has not yet been validated for clinical decision-making. Concomitant medications with substantial pharmacokinetic (PK) interaction with enzalutamide were avoided. Safety and antitumor assessment All patients who received at least one dose of enzalutamide were assessed for safety biweekly for the first 4 weeks, then every 4 weeks until 30 days after the last dose of enzalutamide. Safety and tolerability were determined by assessment of adverse events (AEs), physical examinations, ECOG PS, vital signs, and laboratory tests. The severity of abnormal laboratory values and AEs 17 were classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. SAEs were also evaluated by Astellas Pharma Global Development – United States. A monthly teleconference was held amongst the institutional investigators to review patients and adverse events. An institutional Data Safety and Monitoring Committee at University of Colorado also had oversight for monitoring. Tissue acquisition Fresh tumor biopsies (core needle biopsies of the breast) were required at study entry (BL), and after 4 weeks on therapy (when both Fulv and E were likely at steady state concentrations) and these were termed “W5” biopsy. Fresh frozen and fixed tissue was collected at the time of surgery.

Treatment ID:

TR003445

Treatment Summary:

Study design and treatments NCT02955394 (COMIRB 16-1042) was an open-label randomized phase II trial of fulvestrant with or without enzalutamide. Fulvestrant 500 mg IM was administered on day 1, 15, 29, and then every 4 weeks for a total of 4 months. Enzalutamide 160 mg po daily was given concurrently for 4 months for those women assigned to the combination (Fig. 1A). Surgery was anticipated to occur immediately after week 17, upon completion of enzalutamide; however timing was subject to surgeon and operating suite availability. As drug supply was limited, enzalutamide could not always be continued until the day prior to surgery as originally planned. Stratification factors were institution, clinical node status (N0,N+), and T-stage (T2,T3/4). Pre- or peri-menopausal women received concurrent ovarian suppression with a gonadotropinreleasing hormone agonist. The study was conducted at the Universities of Colorado and Tennessee and Memorial Sloan Kettering Cancer Center. The study protocol and its amendments 16 were approved by the respective Institutional Review Boards as well as the Department of Defence HRPO committee. All patients provided written informed consent prior to participating in the study. The study was conducted under the principles of the World Medical Association, Declaration of Helsinki, and Good Clinical Practice guidelines of the International Conference on Harmonisation. The study did not require an Investigational New Drug Application. Drug support (enzalutamide) was provided by Astellas and Pfizer as part of this investigator-sponsored research study. Study population Eligible patients were women ≥18 years of age with adequate organ and bone marrow function and an ECOG performance score (PS) of 2 or less. All had primary breast cancer of at least 2 cm in size (>T2, N0-2, M0) determined to be ER positive and HER2 negative. Men were excluded due to potential confounding from androgenic stimuli. History of seizures was exclusionary due to the toxicity profile of enzalutamide. Determination of AR expression was not a requirement as it was expected that ~90% of tumors would stain for AR, and the assay has not yet been validated for clinical decision-making. Concomitant medications with substantial pharmacokinetic (PK) interaction with enzalutamide were avoided. Safety and antitumor assessment All patients who received at least one dose of enzalutamide were assessed for safety biweekly for the first 4 weeks, then every 4 weeks until 30 days after the last dose of enzalutamide. Safety and tolerability were determined by assessment of adverse events (AEs), physical examinations, ECOG PS, vital signs, and laboratory tests. The severity of abnormal laboratory values and AEs 17 were classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. SAEs were also evaluated by Astellas Pharma Global Development – United States. A monthly teleconference was held amongst the institutional investigators to review patients and adverse events. An institutional Data Safety and Monitoring Committee at University of Colorado also had oversight for monitoring. Tissue acquisition Fresh tumor biopsies (core needle biopsies of the breast) were required at study entry (BL), and after 4 weeks on therapy (when both Fulv and E were likely at steady state concentrations) and these were termed “W5” biopsy. Fresh frozen and fixed tissue was collected at the time of surgery.