Alisertib +/− Fulvestrant for Breast Cancer

Recruiting at 7 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Fulvestrant

Must not be taking: Proton pump inhibitors

Disqualifiers: Infection, Heart failure, Hypertension, 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

Compensation: Varies

Number of Visits: 34

Duration: Up to 4.5 years

96 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well alisertib with or without fulvestrant works in treating patients with endocrine-resistant breast cancer that has spread to other places in the body. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells or reducing the amount of estrogen made by the body. Giving alisertib with or without fulvestrant may be better in treating patients with breast cancer.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. Specifically, you must stop chemotherapy, immunotherapy, or biologic therapy at least 21 days before, and hormonal therapy at least 14 days before registration. Additionally, you should not be on certain enzyme-inducing drugs or corticosteroids close to the registration date.

What data supports the effectiveness of the drug combination Alisertib and Fulvestrant for breast cancer?

Research shows that Fulvestrant, one of the drugs in the combination, is effective in treating advanced breast cancer, especially in postmenopausal women who have not responded to other treatments like tamoxifen. It works by blocking and degrading estrogen receptors, which are often involved in the growth of breast cancer cells. ^{1 2 3 4 5}

Is the combination of Alisertib and Fulvestrant safe for humans?

Fulvestrant (also known as Faslodex) has been used safely in patients with advanced breast cancer, showing it is generally well-tolerated. However, specific safety data for the combination of Alisertib and Fulvestrant is not provided in the available research. ^{1 2 4 5 6}

How is the drug combination of Alisertib and Fulvestrant unique for breast cancer treatment?

This drug combination is unique because Alisertib is an oral inhibitor targeting Aurora A kinase, which is linked to resistance in estrogen receptor-positive breast cancer, while Fulvestrant is an estrogen receptor antagonist. Together, they may offer a novel approach for patients with endocrine-resistant metastatic breast cancer. ^{1 5 7 8 9}

Research Team

Tufia C. Haddad, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for post-menopausal women with advanced breast cancer that's resistant to hormone therapy. Participants must have ER positive, HER2 negative tumors and can have had no more than two chemotherapy treatments in the metastatic setting. They should not have taken certain medications recently and must be able to swallow pills.

Inclusion Criteria

I had brain cancer spread, treated, no symptoms, and stable scans for 3 months.

I have recovered from my last treatment and can care for myself.

The participant should not be taking certain medications for stomach problems, should limit alcohol, should not have certain heart or sleep issues, should not have certain types of cancer, should be able to understand and agree to take part in the study, should be able to return for follow-up visits, should not have had certain medical procedures or conditions in the past, should be able to swallow pills, should be willing to have a biopsy for research, and should have certain blood and organ function levels within a specific range.

Exclusion Criteria

I haven't had certain treatments or medications within specific days before signing up.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alisertib with or without fulvestrant in 28-day cycles until disease progression or unacceptable toxicity

Up to 4.5 years

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 6 months

Treatment Details

Interventions

• Alisertib
• Fulvestrant

Trial Overview The study is testing alisertib, an enzyme inhibitor thought to slow tumor growth, both alone and combined with fulvestrant, a drug that blocks or reduces estrogen. The goal is to see if one or both drugs together are effective against endocrine-resistant breast cancer.

Participant Groups

Group I: Arm II (alisertib, fulvestrant) Experimental Treatment 3 Interventions

Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (alisertib) Experimental Treatment 2 Interventions

Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.

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

Approved in United States as Alisertib for:

• Acute myeloid leukemia (AML)

Approved in European Union as Alisertib for:

• None approved; under investigation for various cancers

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

In a phase I trial involving 10 postmenopausal patients with endocrine-resistant ER+ metastatic breast cancer, the combination of alisertib and fulvestrant was well tolerated, with no severe toxicities reported during the first treatment cycle.

The treatment showed promising antitumor activity, with a median progression-free survival of 12.4 months and a 6-month clinical benefit rate of 77.8%, indicating potential effectiveness even in patients who had previously progressed on fulvestrant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer. Haddad, TC., D'Assoro, A., Suman, V., et al.[2023]

The combination of alisertib (20 mg twice daily) and docetaxel (75 mg/m²) was found to be safe and well-tolerated in a study involving 41 patients with metastatic cancer, with the recommended phase 2 dose established for future research.

Out of 28 patients evaluated for efficacy, 29% showed objective responses, including one complete response in bladder cancer and several partial responses in prostate cancer and angiosarcoma, indicating potential antitumor activity of the combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. Graff, JN., Higano, CS., Hahn, NM., et al.[2018]

Alisertib, an investigational cancer treatment, showed a 26% increase in total systemic exposure when administered as an oral solution compared to its powder-in-capsule formulation, indicating better bioavailability.

The oral solution of alisertib was absorbed faster than the capsule form, with a quicker peak concentration reached in the bloodstream, suggesting it may be a more effective option for patients who have difficulty swallowing solid medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. Falchook, GS., Venkatakrishnan, K., Sarantopoulos, J., et al.[2015]

References

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

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The future of fulvestrant ("Faslodex"). [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. [2018]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. [2018]

6. Greece pubmed.ncbi.nlm.nih.gov

Fulvestrant for the treatment of advanced breast cancer in postmenopausal women: a Japanese study. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer. [2023]

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

Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. [2015]