TOL2506 + Standard Therapy for Breast Cancer

Enrolling by invitation at 45 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called TOL2506 (Leuprolide Acetate) to determine its safety and effectiveness when combined with standard breast cancer treatments like tamoxifen or aromatase inhibitors. It targets individuals with hormone receptor-positive (HR+), HER2-negative breast cancer. The trial aims to assess whether TOL2506 can help control ovarian function in premenopausal women and men with HR+ breast cancer. Those who completed a previous study with TOL2506 and continue endocrine therapy might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that TOL2506 in combination with standard endocrine therapy is likely to be safe?

Research has shown that TOL2506 has undergone safety testing for breast cancer treatment. Patients who took TOL2506, especially alongside standard treatments like tamoxifen, generally tolerated it well. While some side effects can occur, they are usually mild. Common side effects include hot flashes, headaches, and injection site reactions, similar to those seen with other hormone treatments for breast cancer.

TOL2506 is related to leuprorelin acetate, a treatment commonly used for hormone-receptor-positive breast cancer in premenopausal women, suggesting a good safety record. TOL2506 is in a late-stage trial, indicating some understanding of its safety. Overall, TOL2506 appears to be a promising option with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Unlike the standard of care for breast cancer, which typically involves endocrine therapies like Tamoxifen and Aromatase Inhibitors, TOL2506 is unique because it is combined with these therapies to potentially enhance their effects. Researchers are excited about TOL2506 because it may offer a new mechanism of action that complements existing treatments, potentially improving outcomes for patients. This combination approach could lead to more effective management of breast cancer by targeting the cancer cells in a novel way.

What evidence suggests that TOL2506 in combination with standard endocrine therapy could be effective for breast cancer?

Research has shown that TOL2506, administered with standard endocrine therapy in this trial, can effectively reduce ovarian activity in premenopausal women with HR+ (hormone receptor-positive), HER2-negative breast cancer. One study found that TOL2506 reduced ovarian function six weeks after the first dose. Another study demonstrated that a similar treatment, leuprolide acetate, helped maintain ovarian function in breast cancer patients. This suggests that TOL2506 lowers ovarian activity, which can help control hormone levels and slow cancer growth. These findings support the potential of TOL2506 as a breast cancer treatment. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04906395

Study Details | NCT04906395 | Ovarian Suppression ... This is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23904400/

Effect of leuprolide acetate on ovarian function after ... This study was designed to examine the efficacy of leuprolide acetate on ovarian function preservation in patients with breast cancer.

3. cancer.gov cancer.gov/clinicaltrials/NCT04906395

Ovarian Suppression Evaluating Subcutaneous Leuprolide ... 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- ...

4. cancertherapyadvisor.com cancertherapyadvisor.com/news/extended-release-leuprolide-acetate-in-breast-cancer/

Extended-Release Leuprolide Acetate in Breast Cancer The primary outcome is suppression of ovarian function 6 weeks after the first administration of TOL2506. The secondary outcome is suppression ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.665426/full

Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate ... Our study demonstrated that, in premenopausal patients with HR+ breast cancer, administering a 6M LHRHa formulation after surgery effectively suppressed ovarian ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8064970/

A follow-up study of a randomized controlled ... Adjuvant leuprorelin treatment for ≥ 3 years with tamoxifen only showed similar efficacy and safety profiles to those for 2 years in analyses among all patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5216102/

Efficacy and safety of leuprorelin acetate 6-month depot, TAP ... Leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer.

8. molinahealthcare.com molinahealthcare.com/-/media/Molina/PublicWebsite/PDF/Providers/common/pa-criteria/Leuprolide-long-acting-Lupron-Depot-Eligard-Lupaneta-Lupron-Depot-Ped-C8756-A.pdf

Leuprolide-long-acting-Lupron-Depot-Eligard- ... Premenopausal ovarian suppression in women with breast cancer, Prevention of chemotherapy induced premature ovarian insufficiency, Ovarian cancer ...