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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Anakinra, a medication that blocks certain inflammatory signals, affects breast cancer tumors before surgery. Researchers aim to determine if this treatment alters the tumor environment in patients with early-stage breast cancer, specifically those with triple-negative or low estrogen-receptor-positive types. Participants will either receive Anakinra injections daily for 14 days or continue with their usual care. Suitable candidates have early breast cancer not planned for chemotherapy and have been diagnosed with certain types of breast cancer that do not involve the HER2 protein. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Anakinra is likely to be safe for humans?

Research has shown that anakinra is generally safe for people. In one study, patients with HER2-negative breast cancer received anakinra for several months. Most side effects were mild, and no serious issues required stopping the treatment. Another study found that using anakinra with chemotherapy did not increase side effects compared to chemotherapy alone.

The FDA has already approved anakinra for other uses, indicating that its safety is well understood. Most side effects are mild, such as skin reactions at the injection site. This prior experience with anakinra should reassure those considering joining the trial. ^{1 2 3 4 5}

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

Anakinra is unique because it targets inflammation in a way that current breast cancer treatments typically don't. Most standard treatments, like chemotherapy and hormone therapy, focus on directly attacking cancer cells or blocking hormones that fuel cancer growth. Anakinra, however, is an anti-inflammatory drug that blocks interleukin-1 (IL-1), a protein involved in inflammatory responses, potentially reducing the tumor-promoting inflammation. Researchers are excited because this approach might offer a new way to slow cancer progression and improve outcomes when combined with existing therapies.

What evidence suggests that Anakinra might be an effective treatment for breast cancer?

Research has shown that anakinra, a medication that blocks certain proteins, may help treat breast cancer by reducing tumor inflammation. Studies have found that it can lower inflammation levels around the tumor, which is important for slowing cancer growth. One study found that anakinra effectively shrank breast tumors. In this trial, participants in one group will receive anakinra as an experimental treatment. The FDA has already approved it for other uses, indicating its safety. Early results suggest it could help breast cancer patients by targeting inflammation. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6242808/

An Interleukin-1 Signature in Breast Cancer Treated with ... In addition, treatment with a naturally occurring IL1 receptor antagonist, anakinra, was found to be highly effective in reducing breast tumor ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.e14565

Safety and immunologic activity of anakinra in HER2 ... We hypothesized that anakinra (Ank), an IL-1R antagonist, may decrease tumor inflammation and improve outcomes in MBC patients (pts). Methods: ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9561984/

Novel Methods of Targeting IL-1 Signalling for the Treatment ... Our study shows that the small-molecule inhibitor that targets Caspase-1 has promising anti-tumour effects, inhibiting breast cancer bone ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0024320523009116

Interleukin-1 receptor antagonist: An alternative therapy for ... Significantly, anakinra, the first United States Food and Drug Administration (FDA)-approved IL-1Ra drug, has demonstrated promising antitumor ...

5. targetedonc.com targetedonc.com/view/anakinra-does-not-reduce-crs-or-icans-in-lbcl-treated-with-liso-cel

Anakinra Does Not Reduce CRS or ICANS in LBCL ... Overall response rates (ORR) were 74% in the anakinra cohort vs 80% in the liso-cel alone group, and CR rates were 42% in anakinra-treated ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01802970

Safety and Blood Immune Cell Study of Anakinra Plus ... The objective is to determine the safety of anakinra plus the physician's chemotherapy choice (TPC) of nab paclitaxel, capecitabine, eribulin, or vinorelbine in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1798263/

Safety of extended treatment with anakinra in patients ... Data from the double blind phase of this study were reported previously and showed similar overall frequencies of adverse events and deaths for anakinra treated ...

8. kineretrx.com kineretrx.com/

KINERET® (anakinra) Official Website | Home Children treated with KINERET can experience side effects but in clinical trials, most side effects were mild and no patient had to stop treatment because of ...