TOL2506 + Standard Therapy for Breast Cancer

Recruiting at 24 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Tolmar Inc.

Must be taking: Endocrine therapy, GnRH agonist

Must not be taking: Hormonal therapy, Estrogen

Disqualifiers: Low BMI, Hepatic impairment, others

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: Unknown

Duration: Duration not specified

250 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications, such as oral or transdermal hormonal therapy, estrogen, progesterone, and androgens, as they may impact your safety during the study.

What data supports the effectiveness of the drug TOL2506 in combination with standard therapy for breast cancer?

Leuprolide acetate, a component of TOL2506, has shown antitumor activity in ovarian cancer and is commonly used in prostate cancer, suggesting potential effectiveness in other hormone-sensitive cancers like breast cancer. It was well tolerated in studies, indicating it might be a safe option for patients. ^{1 2 3 4 5}

What makes the drug TOL2506 unique for breast cancer treatment?

TOL2506, also known as leuprolide acetate, is unique because it is a gonadotropin-releasing hormone analogue that can be administered as a long-acting depot injection, which allows for less frequent dosing compared to some other treatments. This drug is commonly used in prostate cancer and has shown potential in treating other hormone-sensitive cancers, suggesting it may offer a novel approach for breast cancer therapy. ^{1 3 4 6 7}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for premenopausal women and men with HR+, HER2- breast cancer who completed the TOL2506A study. Women must be aged 18 to 51, and all participants should consent to continue therapy. Exclusions include severe health issues like poor heart, liver or kidney function, low BMI (<18), high ECOG status (≥3), certain medications that affect safety or response to treatment, and life expectancy less than a year.

Inclusion Criteria

I understand this study is experimental and I agree to participate.

I am a male who has finished Week 48 of the TOL2506A study and can continue hormone therapy.

I finished Week 48 of the TOL2506A study and can continue hormone therapy with ovarian suppression.

Exclusion Criteria

I am a male taking medications that may affect my safety with TOL2506.

I am a man mostly confined to bed or chair due to my health.

My liver tests are not normal, indicating poor liver function.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TOL2506 in combination with standard endocrine therapy (Tamoxifen & Aromatase Inhibitors)

Duration not specified

Safety Extension

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

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Anastrozole Tablets
• Exemestane Tablets
• Letrozole tablets
• Tamoxifen
• TOL2506

Trial Overview The study tests the long-term safety of TOL2506 combined with tamoxifen or an aromatase inhibitor (AI) in suppressing ovarian function in women and endocrine plus GnRH agonist therapy in men for up to four years after completing the initial OVELIA study.

Participant Groups

Group I: TOL2506 Experimental Treatment 5 Interventions

TOL2506 in combination 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 study involving 1,906 patients with advanced prostate cancer, both 3-month and 6-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen (PSA) levels from an average of 12.0 ng/mL to 0.5 ng/mL after 12 months, indicating effective treatment.

The treatment was well-tolerated, with only 8.8% of patients experiencing adverse events, suggesting that leuprorelin acetate is a safe option for managing advanced prostate cancer in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. Ohlmann, CH., Gross-Langenhoff, M.[2018]

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 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 151 men with prostate cancer, the new 6-month leuprolide acetate depot formulation achieved a 93.4% success rate in suppressing testosterone levels to ≤ 50 ng/dl, demonstrating its efficacy in hormone therapy.

The treatment was well tolerated, with sustained testosterone suppression maintained for 12 months and a significant reduction in the frequency of injections needed for patients, improving their overall treatment experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Spitz, A., Young, JM., Larsen, L., et al.[2022]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. [2018]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprorelin acetate 6-month depot in prostate cancer patients: a Phase III, randomized, open-label, parallel-group, comparative study in Japan. [2018]

5. 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]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. [2022]