Safety Extension Study for Subjects With HR+, HER2- Breast Cancer for Subjects Who Have Completed the OVELIA Study

Study Overview
=================
Brief Summary
-----------------
TOL2506A (OVELIA) is a Phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 in suppressing ovarian function in premenopausal women with HR+, HER2-negative breast cancer and men with HR+ breast cancer. The TOL2506A-EXT study described here is a safety extension study to assess and collect long-term data on the ongoing safety and tolerability of TOL2506 in combination with tamoxifen or an AI for up to 4 years.

Official Title
-----------------
Open-label, Safety Extension Study for Subjects With HR+, HER2-Negative Breast Cancer Who Have Completed the OVarian Suppression Evaluating Subcutaneous LeuprolIde Acetate in Breast Cancer OVELIA Study

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: TOL2506
* Drug: Tamoxifen
* Drug: Letrozole tablets
* Drug: Anastrozole Tablets
* Drug: Exemestane Tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females: Completed Visit 9, Week 48 visit of TOL2506A study and is a candidate for continued endocrine therapy + ovarian suppression Able to understand the investigational nature of this study and provide written informed consent prior to the participation in the trial Age 18 to 51 inclusive Exclusion Criteria: Females: Body mass index (BMI) < 18.00 kg/m2 Life expectancy < 12 months ECOG performance status ≥ 3 Unacceptable hepatic function as determined by any of the following: Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN) Aspartate aminotransferase (AST) ≥ 2X ULN Bilirubin ≥ 2X ULN Alkaline phosphatase ≥ 2X ULN Severe hepatic impairment (Child-Pugh Class C) Unacceptable renal function as determined by any of the following: Creatinine ≥ 3X ULN Creatinine clearance ≤ 30 mL/minute Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean Screening 12-lead ECG demonstrating any of the following: Heart rate > 100 beats per minute (BPM) QRS > 120 msec Corrected QT (QTc) > 450 msec PR > 220 msec Use of any new medications known to prolong the QT/QTc interval Any new medical condition or psychiatric, addictive or other disorder that, in the opinion of the Investigator, may interfere with trial conduct or result in the subject being ineligible to continue treatment with TOL2506 Concomitant use of medications that may impact subject safety including but not limited to: Oral or transdermal hormonal therapy Estrogen, progesterone, or androgens Hormonal contraceptives Change in tolerability to TOL2506 that precludes continued treatment Sexually active with a male partner and not willing to use at least 2 non-hormonal contraceptive methods throughout the study Is of childbearing potential with a positive urine pregnancy test at Screening Males: Inclusion Criteria: Completed Visit 9, Week 48 visit of TOL2506A study and is a candidate for continued endocrine + GnRH agonist therapy Able to understand the investigational nature of this study and provide written informed consent prior to participation in the trial Males: Exclusion Criteria: BMI < 18.00 kg/m2 Life expectancy < 12 months ECOG performance status ≥ 3 Unacceptable hepatic function as determined by any of the following: ALT ≥ 2X ULN AST ≥ 2X ULN Bilirubin ≥ 2X ULN Alkaline phosphatase ≥ 2X ULN Severe hepatic impairment (Child-Pugh Class C) Unacceptable renal function as determined by any of the following: Creatinine ≥ 3X ULN Creatinine clearance ≤ 30 mL/minute Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean Screening 12-lead ECG demonstrating any of the following: HR > 100 BPM QRS > 120 msec QTc > 450 msec PR > 220 msec Use of any new medications known to prolong the QT/QTc interval Any new medical condition or psychiatric, addictive or other disorder that, in the opinion of the Investigator, may interfere with trial conduct or result in the subject being ineligible to continue treatment with TOL2506 Concomitant use of medications that may impact subject safety including but not limited to oral or transdermal hormonal therapy Change in tolerability to TOL2506 that precludes continued treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 51 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TOL2506<br>TOL2506 in combination with standard endocrine therapy (Tamoxifen & Aromatase Inhibitors) | Drug: TOL2506<br>* Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months<br>Drug: Tamoxifen<br>* 20 mg once daily or 10 mg 2 times daily - either tablet of solution<br>Drug: Letrozole tablets<br>* One 2.5 mg tablet taken orally once daily<br>Drug: Anastrozole Tablets<br>* One 1 mg tablet taken orally once daily<br>Drug: Exemestane Tablets<br>* One 25 mg tablet taken orally once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrences of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) |  | 4 years from enrolling in study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ovarian Suppression, HR+, HER2-, Oncology, Premenopausal