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Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer (OVELIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04906395
Recruitment Status : Recruiting
First Posted : May 28, 2021
Last Update Posted : January 27, 2023
Sponsor:
Information provided by (Responsible Party):
Tolmar Inc.

Tracking Information
First Submitted Date  ICMJE May 12, 2021
First Posted Date  ICMJE May 28, 2021
Last Update Posted Date January 27, 2023
Actual Study Start Date  ICMJE July 1, 2021
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2022)
Suppression of ovarian function [ Time Frame: 6 weeks after the first administration of TOL2506 ]
LH level < 4 IU/L at Week 6
Original Primary Outcome Measures  ICMJE
 (submitted: May 24, 2021)
Suppression of ovarian function (E2 levels and menses status) [ Time Frame: 6 weeks after the first administration of TOL2506 ]
E2 levels < 20 pg/mL at Week 6 and absence of menses after Week 5
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2022)
  • Suppression of ovarian function overall (LH, E2, menses; treatments pooled) [ Time Frame: 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
  • Suppression of ovarian function overall (LH, E2, menses; TOL2506 + tamoxifen) [ Time Frame: 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
  • Suppression of ovarian function overall (LH, E2; TOL2506 + aromatase inhibitor) [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2021)
  • Suppression of ovarian function overall (E2 and absence of menses; treatments pooled) [ Time Frame: Week 6 to Week 48 ]
    Percent of subjects with suppressed E2 and absence of menses in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) at every measurement from Week 6 to Week 48
  • Suppression of ovarian function overall (E2 and absence of menses; TOL2506 + tamoxifen) [ Time Frame: Week 6 to Week 48 ]
    Percent of subjects with suppressed E2 and absence of menses in subjects treated with TOL2506 + tamoxifen at every measurement from Week 6 to Week 48
  • Suppression of ovarian function overall (E2 and absence of menses; TOL2506 + aromatase inhibitor) [ Time Frame: Week 6 to Week 48 ]
    Percent of subjects with suppressed E2 and absence of menses in subjects treated with TOL2506 + aromatase inhibitor at every measurement from Week 6 to Week 48
  • Suppression of ovarian function at Weeks 12, 24, 36, and 48 (E2 and absence of menses + treatments pooled) [ Time Frame: Weeks 12, 24, 36, and 48 ]
    Percent of subjects with suppressed E2 < 20 pg/mL and absence of menses in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) assessed individually at weeks 12, 24, 36 and 48
  • Suppression of ovarian function at Weeks 12, 24, 36, and 48 (E2 and absence of menses; TOL2506 + tamoxifen) [ Time Frame: Weeks 12, 24, 36, and 48 ]
    Percent of subjects with suppressed E2 < 20 pg/mL and absence of menses in subjects treated with TOL2506 + tamoxifen assessed individually at weeks 12, 24, 36 and 48
  • Suppression of ovarian function at Weeks 12, 24, 36, and 48 (E2 and absence of menses; TOL2506 + aromatase inhibitor) [ Time Frame: Weeks 12, 24, 36, and 48 ]
    Percent of subjects with suppressed E2 < 20 pg/mL and absence of menses in subjects treated with TOL2506 + aromatase inhibitor assessed individually at weeks 12, 24, 36 and 48
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Active Comparator: TOL2506
TOL2506 in combinatination with standard endocrine therapy (Tamoxifen & Aromatase Inhibitors)
Interventions:
  • Drug: TOL2506
  • Drug: Tamoxifen
  • Drug: Letrozole Tablets
  • Drug: Anastrozole Tablets
  • Drug: Exemestane Tablets
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 24, 2021)
250
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2024
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    1. Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN)
    2. Aspartate aminotransferase (AST) ≥ 2X ULN
    3. Bilirubin ≥ 2X ULN
    4. Alkaline phosphatase ≥ 2X ULN
    5. Severe hepatic impairment (Child-Pugh Class C)
  6. Unacceptable renal function as determined by any of the following:

    1. Creatinine ≥ 3X ULN
    2. Creatinine clearance ≤ 30 mL/minute
    3. Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean
  7. History of significantly abnormal ECG or screening 12-lead ECG demonstrating any of the following:

    1. HR > 100 BPM
    2. QRS > 120 msec
    3. QTc > 450 msec
    4. PR > 220 msec
  8. Prior (within 28 days prior to Day 1) and/or concomitant use of medications known to prolong the QT/QTc interval
  9. 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
  10. Concomitant use of anticancer mediations other than those specified for use by the protocol
  11. Prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer
  12. History of treatment for osteopenia/osteoporosis
  13. 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
  14. 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)
  15. 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)
  16. 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
  17. Already receiving and/or previously received GnRH analogs within 1 year before breast cancer diagnosis
  18. Psychiatric, addictive, or other disorders that would preclude study compliance
  19. Use of medications that may impact subject safety and/or affect the PK of the drug and hormonal assessments including but not limited to:

    1. Oral or transdermal hormonal therapy within 30 days prior to subject's first visit
    2. Estrogen, progesterone, or androgens within 30 days prior to subject's first visit
    3. Hormonal contraceptives within 30 days prior to subject's first visit
    4. Medications known to result in clinically important decreases in bone mass taken within 6 months prior to subject's first visit
  20. Known hypersensitivity, idiosyncratic, or allergic reactions to GnRH, GnRH agonist/analogs or to any of the components of the IP
  21. Sexually active with a male partner and not willing to use non-hormonal contraceptive methods throughout the study
  22. Is of childbearing potential with a positive serum pregnancy test at Screening or urine pregnancy test at Day 1
  23. 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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 49 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: A Mehta 919-589-2121 ext 2121 amehta@clinipace.com
Contact: E Rielage 937-598-2940 erielage@clinipace.com
Listed Location Countries  ICMJE Mexico,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04906395
Other Study ID Numbers  ICMJE TOL2506A
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Tolmar Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Tolmar Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: E P Hamilton SCRI Development Innovations, LLC
PRS Account Tolmar Inc.
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP