Ovarian Suppression Therapy for Breast Cancer

(OVELIA Trial)

Recruiting at 82 trial locations

Overseen By Kerlin Lynch

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Tolmar Inc.

Must be taking: Endocrine therapy

Must not be taking: SERMs, mTOR inhibitors

Disqualifiers: BMI, Breastfeeding, Life expectancy, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 48 weeks

250 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications, but it does mention that you cannot use certain hormonal therapies, anticancer medications, or drugs that affect bone density or the QT/QTc interval. It's best to discuss your current medications with the trial team to see if any need to be stopped.

What data supports the effectiveness of the drug TOL2506 for breast cancer?

Research shows that leuprolide acetate, a component of TOL2506, was effective in treating metastatic breast cancer in premenopausal women, with 44% experiencing a partial response and 20% having stable disease. This suggests potential effectiveness for TOL2506 in similar conditions. ^{1 2 3 4 5}

Is ovarian suppression therapy with leuprolide acetate generally safe for humans?

Leuprolide acetate, used in various formulations for different conditions, has been generally well tolerated in clinical studies. Common side effects include hot flashes and mild swelling, but no serious adverse effects were observed in studies involving prostate cancer patients. ^{1 2 6 7 8}

How is the drug TOL2506 different from other treatments for breast cancer?

TOL2506, also known as leuprolide acetate, is unique because it is a gonadotropin-releasing hormone analogue that works by suppressing ovarian function, which can be beneficial in hormone-sensitive breast cancer. Unlike traditional chemotherapy, it is administered as a depot injection, which means it is given less frequently and can be more convenient for patients. ^{1 3 4 9 10}

What is the purpose of this trial?

This trial tests TOL2506, a treatment that stops ovaries from working, in premenopausal women and men with hormone-sensitive breast cancer. It aims to reduce hormone levels to slow down or stop cancer growth. TOL2506 is a treatment that stops ovaries from working, similar to other ovarian suppression methods.

Research Team

E P Hamilton

Principal Investigator

SCRI Development Innovations, LLC

Eligibility Criteria

This trial is for premenopausal women aged 18-49 with HR+, HER2-negative breast cancer who are candidates for endocrine therapy and ovarian suppression. Men with the same cancer type may also participate. Participants must have normal liver, kidney function, and not be on certain medications or treatments that could interfere with the study.

Inclusion Criteria

Your follicle stimulating hormone (FSH) level is less than 40 IU/L.

I have regular menstrual cycles or confirmed premenopausal status.

My breast cancer is early to mid-stage, hormone receptor positive, and HER2 negative.

Exclusion Criteria

I haven't used tamoxifen, SERMs, aromatase inhibitors, mTOR inhibitors, or hormone therapy in the 3 months before my breast cancer diagnosis.

I have received hormone therapy for breast cancer since my diagnosis.

I haven't taken drugs or supplements for bone density in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial and full screening visits

Treatment

Participants receive TOL2506 in combination with endocrine therapy for ovarian suppression

48 weeks

Regular visits for dosing and monitoring at Weeks 6, 12, 24, 36, and 48

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Safety Extension

Participants may be eligible to participate in a Safety Extension Study under a separate protocol

Treatment Details

Interventions

• TOL2506

Trial Overview The effectiveness of TOL2506 in suppressing ovarian function alongside standard therapies (tamoxifen or aromatase inhibitors) is being tested over a 48-week period. The study will assess if this treatment can maintain low estradiol levels in women and testosterone levels in men.

Participant Groups

Group I: Active Comparator: TOL2506 Experimental Treatment 5 Interventions

TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors)

TOL2506 is already approved in United States, European Union for the following indications:

Approved in United States as Eligard for:

• Advanced prostate cancer
• Central precocious puberty
• Endometriosis
• Anemia caused by uterine fibroids

Approved in European Union as Eligard for:

• Prostate cancer
• Precocious puberty
• Endometriosis
• Uterine fibroids

Who Is Running the Clinical Trial?

Tolmar Inc.

Lead Sponsor

Trials

5

Recruited

1,400+

Findings from Research

In a study of 23 patients with refractory epithelial ovarian cancer, leuprolide acetate showed a partial response in 17% of patients, particularly among those with grade 1 carcinomas, with a median response duration of 52 weeks.

The treatment was well tolerated, with only mild side effects reported, suggesting that leuprolide acetate could be a safe option for patients with certain types of ovarian cancer, warranting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leuprolide acetate in the treatment of refractory or persistent epithelial ovarian cancer. Kavanagh, JJ., Roberts, W., Townsend, P., et al.[2017]

In a 12-month study involving 111 patients with prostate cancer, the new 6-month subcutaneous depot of leuprolide acetate (LA-2585) effectively suppressed serum testosterone levels to below the medical castrate threshold of 50 ng/dl in 99% of patients by the end of the study.

LA-2585 was found to be safe, with no significant flare reactions and only mild to moderate hot flashes reported as common side effects, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer. Crawford, ED., Sartor, O., Chu, F., et al.[2022]

Leuprolide acetate, a hormone therapy, showed beneficial effects in five patients with ovarian carcinoma, particularly those who had previously failed intensive chemotherapy.

The study suggests that patients with refractory ovarian carcinoma, who typically have limited treatment options due to resistance to hormone therapy and other clinical conditions, may benefit from expanded eligibility for hormonal treatments like leuprolide acetate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced refractory ovarian carcinoma with a gonadotropin-releasing hormone analogue. Bruckner, HW., Motwani, BT.[2019]

In a study of 25 patients with advanced ovarian cancer, leuprolide acetate showed limited efficacy, with only 4% achieving a partial response and 60% maintaining stable disease for at least 8 weeks.

The treatment was well tolerated, with no life-threatening side effects, although mild toxicities such as leukopenia and gastrointestinal issues were reported in a small number of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of leuprolide acetate in patients with advanced epithelial ovarian carcinoma. A Gynecologic Oncology Group study. Miller, DS., Brady, MF., Barrett, RJ.[2019]

In a study of 26 premenopausal women with metastatic breast cancer, leuprolide (a gonadotropin-releasing hormone analogue) resulted in a 44% partial response rate, with a median response duration of 39 weeks.

Leuprolide was found to be safe, with mild side effects such as hot flashes and nausea, and it effectively induced amenorrhea in all patients treated for ten weeks or longer, indicating its potential for medical castration in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. Harvey, HA., Lipton, A., Max, DT., et al.[2017]

The 6-month GnRH agonist depot formulations, leuprolide acetate 45 mg and triptorelin pamoate 22.5 mg, are effective for palliative treatment of advanced prostate cancer, achieving chemical castration rates of 93% to 99%, while also improving patient convenience by reducing the frequency of injections.

Both formulations have a safety profile similar to existing treatments, with hot flashes being the most common side effect, suggesting they can be effectively integrated with other cancer treatments like surgery and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort. Crawford, ED., Phillips, JM.[2023]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[2023]

The new 3-month depot formulation of leuprolide acetate (Luphere 3M Depot) demonstrated a high encapsulation efficiency of 94.7% and a delayed release profile similar to the existing Lucrin Depot, indicating effective drug delivery.

In a study involving 20 prostate cancer patients, both Luphere 3M and Lucrin Depot were well tolerated with no serious adverse effects, showing comparable safety and pharmacokinetics between the two formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative in vitro release and clinical pharmacokinetics of leuprolide from Luphere 3M Depot, a 3-month release formulation of leuprolide acetate. Park, S., Kim, DH., Kim, Y., et al.[2017]

In a study of 32 patients with relapsed epithelial ovarian cancer who had exhausted standard treatments, Leuprolide acetate showed significant activity as a salvage therapy, with 12.5% of patients achieving a partial response lasting an average of 8.7 months.

The treatment was well-tolerated with no reported toxicity, highlighting its potential as a safe option for patients who have limited alternatives after platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leuprolide acetate as a salvage-therapy in relapsed epithelial ovarian cancer. Marinaccio, M., D'Addario, V., Serratì, A., et al.[2020]

In a study of 19 poor responders undergoing IVF, pretreatment with oral contraceptive pills (OCPs) significantly lowered baseline FSH levels before a 1 mg Lupron injection, indicating a potential benefit in managing hormone levels prior to treatment.

While both groups experienced an increase in FSH and LH after Lupron administration, the OCP-pretreated group had a significantly lower rise in LH, which may help in optimizing the IVF flare protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of FSH flare with and without pretreatment with oral contraceptive pills in poor responders undergoing in vitro fertilization. Keltz, MD., Gera, PS., Skorupski, J., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Leuprolide acetate in the treatment of refractory or persistent epithelial ovarian cancer. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of advanced refractory ovarian carcinoma with a gonadotropin-releasing hormone analogue. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of leuprolide acetate in patients with advanced epithelial ovarian carcinoma. A Gynecologic Oncology Group study. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. [2017]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Comparative in vitro release and clinical pharmacokinetics of leuprolide from Luphere 3M Depot, a 3-month release formulation of leuprolide acetate. [2017]

9. Singapore pubmed.ncbi.nlm.nih.gov

Leuprolide acetate as a salvage-therapy in relapsed epithelial ovarian cancer. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Comparison of FSH flare with and without pretreatment with oral contraceptive pills in poor responders undergoing in vitro fertilization. [2013]