Hormone Therapy for Breast Cancer

Not currently recruiting at 3 trial locations

Overseen By Ohio State University Comprehensive Cancer Center

Age: 65+

Sex: Female

Trial Phase: Phase 2

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Aromatase inhibitors, Metastases, Psychiatric illness, 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: Unknown

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining two drugs, fulvestrant and palbociclib, for treating certain types of breast cancer in patients who cannot undergo surgery. Fulvestrant, a hormone therapy, blocks estrogen to halt cancer growth, while palbociclib prevents cancer cells from multiplying. The trial aims to determine if these drugs together can effectively treat breast cancer that responds to hormone therapy. It may suit patients with newly diagnosed estrogen or progesterone-positive breast cancer who are frail or vulnerable and have opted against surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking strong inducers or inhibitors of CYP3A4 (a liver enzyme that affects drug metabolism).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of fulvestrant and palbociclib is generally well-tolerated by patients. One study found that the most common serious side effects involved changes in blood cell counts. Specifically, about 56% of participants experienced a significant drop in neutrophils (grade 3 neutropenia), and 11% experienced an even more severe drop (grade 4). Additionally, 30% had a significant decrease in overall white blood cells (grade 3 leukopenia).

Palbociclib, when used with fulvestrant, already has FDA approval for treating certain types of breast cancer. This approval indicates a known safety profile, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Fulvestrant and palbociclib stand out because they combine to target breast cancer in a unique way. While traditional treatments often focus solely on hormone receptors, this duo tackles two fronts: fulvestrant blocks estrogen receptors, and palbociclib inhibits specific proteins called CDK4/6 that cancer cells need to grow. This dual-action approach could slow cancer progression more effectively than standard hormone therapies alone. Researchers are excited because this combination has the potential to offer better control over the disease with a manageable side effect profile, giving patients a promising new option.

What evidence suggests that fulvestrant and palbociclib might be an effective treatment for hormone responsive breast cancer?

Studies have shown that combining fulvestrant and palbociclib effectively treats estrogen-receptor-positive breast cancer. Research indicates that this combination can extend patients' lives compared to using fulvestrant alone. One study found that patients lived about 6.9 months longer with both drugs. Another analysis revealed that the cancer took about 7.43 months longer to worsen. In this trial, participants will receive both fulvestrant and palbociclib, which together have shown promise as a strong option for managing this type of breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Nicole O Williams, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for older patients with hormone-responsive breast cancer that can't be surgically removed. Participants must have normal levels of bilirubin, creatinine, and liver enzymes, not have had prior aromatase inhibitor therapy or strong CYP3A4 drugs, and no distant metastases. They should also meet certain health criteria indicating they are vulnerable or frail according to Balducci Criteria.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I am considered vulnerable or frail due to health issues, or I am refusing breast surgery.

I have chosen not to undergo surgery for my breast cancer, as noted by my surgeon and oncologist.

Exclusion Criteria

My cancer has spread to distant parts of my body.

Psychiatric illness, which would prevent the patient from giving informed consent

I am not taking medication that strongly affects liver enzyme CYP3A4.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fulvestrant intramuscularly on days 1 and 15 and palbociclib orally once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Palbociclib

Trial Overview The study tests the effectiveness of combining fulvestrant (a hormone therapy) with palbociclib (an enzyme blocker) in treating estrogen-receptor-positive breast cancer. The goal is to see if this combination helps stop tumor growth by blocking estrogen use and cell growth enzymes.

How Is the Trial Designed?

Group I: Treatment (fulvestrant, palbociclib) Experimental Treatment 5 Interventions

Patients receive fulvestrant IM on days 1 and 15. Patients also receive palbociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

In a study involving 1723 women with HR+/HER2- advanced or metastatic breast cancer, palbociclib combined with aromatase inhibitors or fulvestrant showed low dose-reduction rates (18.9% and 12.3%, respectively), indicating good tolerability.

The treatment demonstrated favorable progression-free rates (PFR) at 12 months, with 88.1% for palbociclib + AI and 79.8% for palbociclib + fulvestrant, along with high survival rates (97.3% and 97.5%, respectively), suggesting its effectiveness in real-world clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. Mycock, K., Zhan, L., Hart, K., et al.[2022]

In a study of 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

The FDA approved palbociclib (IBRANCE) for use in men with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, expanding its indications beyond women, based on data from the PALOMA-2 and PALOMA-3 trials.

The approval was supported by safety data from phase I studies and real-world evidence, confirming that palbociclib is a viable treatment option for male patients with this type of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. Wedam, S., Fashoyin-Aje, L., Bloomquist, E., et al.[2021]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8859011/

Real-world effectiveness of palbociclib plus fulvestrant in ... Palbociclib plus fulvestrant seems to be an effective therapy for ABC in real-world. · Median rwPFS and rwOS were estimated at 7.43 and 24.70 months, ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1810527

Overall Survival with Palbociclib and Fulvestrant in ... Taken together, the data from the PALOMA-3 trial showed that palbociclib in combination with fulvestrant led to a 6.9-month prolongation of ...

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01178-0/fulltext

Extended follow-up of palbociclib with fulvestrant or ... No significant difference in OS or PFS between fulvestrant and letrozole when combined with palbociclib was observed. Median OS was 61.8 months, and median PFS ...

4. breastcancer.org breastcancer.org/research-news/ibrance-faslodex-combo-continues-to-improve-overal-survival-in-advanced-hr-positive

Ibrance-Faslodex Combo Continues To Improve Overall ... The latest results from the PALOMA-3 trial show that combining Ibrance and Faslodex continues to offer better overall survival than Faslodex alone.

5. academic.oup.com academic.oup.com/oncolo/article/30/7/oyae291/7852806

Real-world effectiveness of palbociclib plus endocrine therapy ... The effectiveness of palbociclib-based regimens was also assessed in the per-label population, representing 861 out of 1250 patients (68.9%) in ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00994

Final Overall Survival in the Phase III FALCON Trial The randomized phase III FALCON trial demonstrated significant improvement in progression-free survival (PFS) with fulvestrant versus ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625005867

Palbociclib treatment in patients with HR+/HER2− ... Utilizing Surveillance, Epidemiology, and End Results (SEER) registry data, Brufsky et al. reported a 48-month breast cancer-specific survival rate of 44.5 % in ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/22/20/4968/124844/FDA-Approval-of-Palbociclib-in-Combination-with

FDA Approval of Palbociclib in Combination with Fulvestrant ... Safety results​​ The most common (≥5%) grade ≥3 AEs in the palbociclib plus fulvestrant arm were neutropenia (56% grade 3, 11% grade 4), and leukopenia (30% ...