Anakinra for Breast Cancer

(OZM-034 Trial)

Recruiting at 1 trial location

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: IL-1 antagonists

Must not be taking: Glucocorticoids

Disqualifiers: Male, HER2 positive, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

50 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using glucocorticoids above a certain dose, you may need to adjust your medication before starting the trial.

How does the drug Anakinra differ from other breast cancer treatments?

Anakinra is unique because it is primarily used to treat inflammatory conditions like rheumatoid arthritis by blocking interleukin-1 (a protein that causes inflammation), whereas most breast cancer treatments focus on hormone suppression or chemotherapy. This novel approach may offer a different mechanism of action compared to traditional breast cancer therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

This study will examine changes in the tumor microenvironment (TME) induced by 14 days of pre-operative IL-1-inhibiting therapy among patients with early breast cancer (including TNBC and ER-low positive). Key immune biomarkers (TILs, TAMs, NK cells, IL1\[beta\] and inflammasome component expression) will be evaluated at baseline and following 14 days of IL-1 antagonist therapy (Anakinra) using paired tissue specimens.

Eligibility Criteria

This trial is for patients with early-stage breast cancer, including triple-negative and ER-low positive types. Participants should be scheduled for pre-operative therapy and willing to undergo tissue sampling before and after a 14-day treatment period.

Inclusion Criteria

I am not scheduled for chemotherapy before surgery.

My breast cancer is early stage, not spread, and either triple-negative or has low estrogen receptors.

I am older than 18 years.

Exclusion Criteria

Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening or 5 half-lives (whichever is longer) prior to the first dose of investigational product

Significant concurrent, uncontrolled medical condition which, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol

Known hypersensitivity to E-coli derived proteins, Anakinra or any component of the product

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Anakinra SC injection 100mg daily for 14 days

2 weeks

Follow-up

Participants are monitored for changes in the tumor microenvironment and immune biomarkers

4 weeks

Treatment Details

Interventions

• Anakinra

Trial Overview The study tests the effects of Anakinra, an IL-1 inhibitor, on the tumor microenvironment over two weeks prior to surgery. It focuses on how this drug changes immune biomarkers within the tumor.

Participant Groups

Group I: Group 1 Experimental Treatment 1 Intervention

Anakinra SC injection 100mg daily x 14 days

Group II: Group 2 Active Control 1 Intervention

Patients will receive standard of care treatment

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

Approved in European Union as Kineret for:

• Rheumatoid arthritis
• Cryopyrin-associated periodic syndromes
• Deficiency of interleukin-1 receptor antagonist
• COVID-19

Approved in United States as Kineret for:

• Rheumatoid arthritis
• Deficiency of interleukin-1 receptor antagonist
• Neonatal-onset multisystem inflammatory disease (NOMID)
• COVID-19

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[2018]

Endocrine therapy is the first-line treatment for patients with ER-positive metastatic breast cancer, with tamoxifen being a long-standing option, but newer agents like anastrozole have shown equivalent efficacy and better side effects, making them viable first-line choices for postmenopausal women.

Anastrozole and letrozole are effective second-line therapies after tamoxifen failure, and exemestane has shown efficacy as a second and even third-line treatment, indicating a range of options for managing metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy in the treatment of metastatic breast cancer. Buzdar, AU.[2019]

Anastrozole is an effective alternative to tamoxifen for treating hormone-responsive breast cancer in postmenopausal women, showing superior efficacy and tolerability in early breast cancer.

As a third-generation aromatase inhibitor, anastrozole effectively suppresses estrogen production with minimal effects on other enzymes, lipid profiles, or steroid hormone production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The adjuvant endocrine treatment revolution: focus on anastrozole. Jakesz, R.[2019]

In a study involving 764 postmenopausal women with advanced breast cancer, anastrozole (1 mg daily) showed a significant survival advantage over megestrol acetate, with a median time to death of 26.7 months compared to 22.5 months for megestrol acetate.

Anastrozole also demonstrated higher 2-year survival rates (56.1% for 1 mg and 54.6% for 10 mg) compared to megestrol acetate (46.3%), indicating its efficacy as a treatment option after disease progression with tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Arimidex Study Group. Buzdar, AU., Jonat, W., Howell, A., et al.[2022]

Anastrozole, letrozole, and exemestane are effective nonsteroidal aromatase inhibitors for treating advanced breast cancer in postmenopausal women, with anastrozole showing the highest selectivity and minimal impact on lipid levels.

Exemestane is associated with androgenic side effects and has a shorter half-life compared to letrozole, which has a longer time to reach steady-state plasma levels, indicating important differences in their pharmacokinetics and potential long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane. Buzdar, AU., Robertson, JF., Eiermann, W., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. [2018]

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

Endocrine therapy in the treatment of metastatic breast cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

The adjuvant endocrine treatment revolution: focus on anastrozole. [2019]

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

Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Arimidex Study Group. [2022]

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

An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane. [2022]