OVELIA: Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer

• Sponsor: Tolmar Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04906395
• Collaborator: (none)
• Enrollment: 250
• Locations: 24
• Arm: 1
• Anticipated Duration (Months): 36
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. The study will also aim to assess the safety of TOL2506 in men with HR+ breast cancer. The Screening Period will be conducted in two parts: 1) an abbreviated, initial screening where premenopausal status will be determined prior to neoadjuvant or adjuvant chemotherapy (if planned) and 2) the full screening assessment conducted after neoadjuvant or adjuvant chemotherapy (or for subjects who enter the study without having received chemotherapy). Following the Screening Period, eligible subjects will enter into the 48 week Treatment Period in 1 of 2 groups: those who will receive tamoxifen concurrently with TOL2506 or those who will initiate therapy with an AI (letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, upon confirmation that estradiol (E2) levels of < 20 pg/mL have been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the discretion of the Investigator. However, a switch is not permitted 28 days prior to a dosing visit (eg, Week 24, 36, and 48 where a pre-dose blood sample for PK and PD analysis will be drawn). At the end of the Treatment Period, upon completion of the End of Study Visit (Visit 9, Week 48) subjects may be eligible to participate in a Safety Extension Study under a separate Protocol.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: TOL2506; Drug: Tamoxifen; Drug: Letrozole Tablets; Drug: Anastrozole Tablets; Drug: Exemestane Tablets	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 250 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 3,Single Arm,Open-Label Study Evaluating Ovarian Suppression Following 3 Month Leuprolide Acetate For Injectable Suspension (TOL2506) in Combination With Endocrine Therapy in Premenopausal Subjects With Hormone-Receptor-Positive (HR+),Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
• Actual Study Start Date: Jul 1, 2021
• Anticipated Primary Completion Date: Jun 30, 2024
• Anticipated Study Completion Date: Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Comparator: TOL2506 TOL2506 in combinatination with standard endocrine therapy (Tamoxifen & Aromatase Inhibitors)	Drug: TOL2506; Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months.; Drug: Tamoxifen; 20 mg once daily or 10 mg 2 times daily - either tablet or solution; Drug: Letrozole Tablets; One 2.5 mg tablet taken orally once daily; Drug: Anastrozole Tablets; One 1 mg tablet taken orally once daily; Drug: Exemestane Tablets; One 25 mg tablet taken orally once daily

Outcome Measures

Primary Outcome Measures

1. Suppression of ovarian function [6 weeks after the first administration of TOL2506]

   LH level < 4 IU/L at Week 6

Secondary Outcome Measures

1. Suppression of ovarian function overall (LH, E2, menses; treatments pooled) [Week 6 to Week 48]

   Percent of all subjects with LH < 4 IU/L, E2 <20 pg/mL in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) at every measurement from Week 6 to Week 48

2. Suppression of ovarian function overall (LH, E2, menses; TOL2506 + tamoxifen) [Week 6 to Week 48]

   Percent of all subjects with LH < 4 IU/L, E2 <20 pg/mL in subjects treated with TOL2506 + tamoxifen at every measurement from Week 6 to Week 48

3. Suppression of ovarian function overall (LH, E2; TOL2506 + aromatase inhibitor) [Week 6 to Week 48]

   Percent of all subjects with LH < 4 IU/L, E2 <20 pg/mL in subjects treated with TOL2506 + aromatase inhibitor at every measurement from Week 6 to Week 48

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Female

1. Able to understand the investigational nature of this study and provide written informed consent prior to the participation in the trial

2. Age 18 to 49, inclusive

3. Diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER>1% and/or, PR>1%, HER2-negative per ASCO CAP guidelines)

4. Is a candidate for endocrine therapy + ovarian suppression LH > 4 IU/L within 28 days prior to Day 1

5. Is premenopausal as defined by:

• E2 > 30 pg/mL

• follicle stimulating hormone (FSH) < 40 IU/L

• regular menses (eg, menstrual cycle length of 21 to 35 days) Note: premenopausal status must be determined before neo/adjuvant chemotherapy in patients for which it is planned or prior to Day 1 in patients who did not have prior chemotherapy. If premenopausal status was not determined prior to chemotherapy, E2 and FSH must meet the above criteria when measured 2 weeks or more after the end of the final cycle of chemotherapy.

Exclusion Criteria:

1. Body mass index (BMI) < 18.00 kg/m2 or > 35.00 kg/m2

2. Breastfeeding

3. Life expectancy < 12 months

4. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3

5. Unacceptable hepatic function as determined by any of the following:

6. Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN)

7. Aspartate aminotransferase (AST) ≥ 2X ULN

8. Bilirubin ≥ 2X ULN

9. Alkaline phosphatase ≥ 2X ULN

10. Severe hepatic impairment (Child-Pugh Class C)

11. Unacceptable renal function as determined by any of the following:

12. Creatinine ≥ 3X ULN

13. Creatinine clearance ≤ 30 mL/minute

14. Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean

15. History of significantly abnormal ECG or screening 12-lead ECG demonstrating any of the following:

16. HR > 100 BPM

17. QRS > 120 msec

18. QTc > 450 msec

19. PR > 220 msec

20. Prior (within 28 days prior to Day 1) and/or concomitant use of medications known to prolong the QT/QTc interval

21. Prior use of tamoxifen, other SERMs (eg, raloxifene) or antagonists (eg, fulvestrant), aromatase inhibitor, mammalian target of rapamycin (mTOR) inhibitors, or hormone replacement therapy within 3 months before breast cancer diagnosis

22. Concomitant use of anticancer mediations other than those specified for use by the protocol

23. Prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer

24. History of treatment for osteopenia/osteoporosis

25. Prior (within 6 months prior to Day 1) or current use of drugs known to increase bone mineral density (ie, bisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab) or use of supplements known to increase bone mineral density (ie, calcitonin, fluoride, strontium) within 28 days prior to Day 1

26. Low trauma fracture(s) occurring within 12 months prior to subject's first visit (defined as a fracture that results from a fall from a standing height or less, excluding fingers, toes, face and skull)

27. Conditions that preclude bone mineral density measurement (lumbar spine/bilateral hip surgery with hardware in place, abdominal clips, umbilical ring [not willing to remove] or weight that exceeds the DEXA machine limitation)

28. Any other medical condition or serious illness, presence of a second malignancy under current treatment or follow-up, or the presence of clinically significant findings on the physical exam, laboratory testing, medical history (including conditions that may be associated with low bone mass), that in the opinion of the Investigator may interfere with trial conduct, subject safety, or interpretation of study results

29. Already receiving and/or previously received GnRH analogs within 1 year before breast cancer diagnosis

30. Psychiatric, addictive, or other disorders that would preclude study compliance

31. Use of medications that may impact subject safety and/or affect the PK of the drug and hormonal assessments including but not limited to:

32. Oral or transdermal hormonal therapy within 30 days prior to subject's first visit

33. Estrogen, progesterone, or androgens within 30 days prior to subject's first visit

34. Hormonal contraceptives within 30 days prior to subject's first visit

35. Medications known to result in clinically important decreases in bone mass taken within 6 months prior to subject's first visit

36. Known hypersensitivity, idiosyncratic, or allergic reactions to GnRH, GnRH agonist/analogs or to any of the components of the IP

37. Sexually active with a male partner and not willing to use non-hormonal contraceptive methods throughout the study

38. Is of childbearing potential with a positive serum pregnancy test at Screening or urine pregnancy test at Day 1

39. Exposure to any investigational agent within 30 days prior to the first dose of TOL2506

See contact information to obtain inclusion/exclusion criteria for males

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marin Cancer Care, Inc	Greenbrae	California	United States	94904
2	Holy Cross Hospital - Bienes Cancer Center	Fort Lauderdale	Florida	United States	33308
3	BRCR Medical Cancer Center Inc.	Plantation	Florida	United States	33322
4	Northwestern Medicine Cancer Center	Warrenville	Illinois	United States	60555
5	Cancer Center of Kansas	Wichita	Kansas	United States	67214
6	Baptist Health Lexington	Lexington	Kentucky	United States	40503
7	Baptist Health Louisville	Louisville	Kentucky	United States	40207
8	Hematology Oncology Clinic	Baton Rouge	Louisiana	United States	70809
9	University of Maryland, St. Joseph Medical Center, Cancer Institute	Towson	Maryland	United States	21093
10	Revive Research Institute, Inc.	Farmington Hills	Michigan	United States	48334
11	Revive Research Institute, Inc.	Sterling Heights	Michigan	United States	48314
12	Washington University School of Medicine, Center for Advanced Medicine	Saint Louis	Missouri	United States	63110
13	St. Vincent - Frontier Cancer Center	Billings	Montana	United States	59102
14	Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park	Bronx	New York	United States	10461
15	Hematology Oncology Associates of Central New York, PC	East Syracuse	New York	United States	13057
16	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
17	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
18	MUSC Hollings Cancer Center- HCC	Charleston	South Carolina	United States	29425
19	Tennessee Oncology, PLLC	Chattanooga	Tennessee	United States	37404
20	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
21	Oncology & Hematology of South Texas, PA	Laredo	Texas	United States	78041
22	Joe Arrington Cancer Research & Treatment Center	Lubbock	Texas	United States	79410
23	Seattle Cancer Center Alliance	Seattle	Washington	United States	98109
24	FDI Clinical Research	San Juan		Puerto Rico	00927

Sponsors and Collaborators

• Tolmar Inc.

Investigators

• Principal Investigator: E P Hamilton, SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tolmar Inc.
• ClinicalTrials.gov Identifier: NCT04906395
• Other Study ID Numbers: TOL2506A
• First Posted: May 28, 2021
• Last Update Posted: Jul 19, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tolmar Inc.: Ovarian Suppression; HR+; HER2-; Oncology; Premenopausal
• Additional relevant MeSH terms: Breast Neoplasms; Tamoxifen; Letrozole; Anastrozole; Exemestane

Study Results

No Results Posted as of Jul 19, 2022