Palbociclib + Fulvestrant for Breast Cancer

Not currently recruiting at 6 trial locations

Overseen By Kimmel Cancer Center Clinical Research Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Palbociclib, Aromatase inhibitors

Must not be taking: CYP3A4 inhibitors, QTc prolongers

Disqualifiers: Pregnancy, Severe cardiac event, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, palbociclib (Ibrance) and fulvestrant (Faslodex), to determine their effectiveness in treating breast cancer that has progressed after initial therapy. The researchers aim to understand if continuing palbociclib with fulvestrant better controls the disease. Women with advanced breast cancer that cannot be treated with surgery or radiation, particularly those whose cancer has estrogen or progesterone receptors but not the HER2 protein, may be suitable if their disease has progressed after prior treatments. 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 use drugs that affect CYP3A4 or prolong the QTc interval. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of palbociclib and fulvestrant is generally safe and well-tolerated for patients with a specific type of advanced breast cancer. This combination has been studied before, and most patients managed it well. However, some side effects appeared, such as low white blood cell counts, which can affect the immune system, and low platelet counts, which can affect blood clotting. These side effects were observed in both clinical trials and real-world settings.

Prospective trial participants should discuss these possible side effects with their doctor. The doctor can help understand how to manage any risks and ensure safety during the trial. ^{1 2 3 4 5}

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

Researchers are excited about Palbociclib combined with Fulvestrant for treating breast cancer because it works differently than standard treatments. Most current therapies focus on directly killing cancer cells, but Palbociclib inhibits specific proteins known as CDK4/6, which are crucial for cancer cell division and growth. This targeted approach can potentially slow down the cancer's progression with more precision and potentially fewer side effects compared to traditional chemotherapy. By pairing Palbociclib with Fulvestrant, which blocks estrogen receptors, this combination aims to attack breast cancer from multiple angles, offering hope for improved outcomes.

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

Research has shown that combining palbociclib with fulvestrant effectively treats advanced breast cancer. In the PALOMA-3 study, this combination increased overall survival by 6.9 months compared to fulvestrant alone. Real-world data indicates that this combination results in a median time of 7.43 months before cancer worsens and an overall survival of 24.70 months. This treatment improves outcomes for patients whose cancer has progressed after previous treatments. These findings suggest that continuing with palbociclib and fulvestrant offers a promising approach to managing breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Jessica Tao, MD

Principal Investigator

SKCCC Johns Hopkins Medical Institution

Vered Stearns, M.D.

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for women with metastatic or advanced breast cancer that worsened after at least 6 months of palbociclib and an aromatase inhibitor. They must have had no more than one chemotherapy for advanced disease, no prior fulvestrant or certain other treatments, and should be in a stable condition if they've had brain metastasis or recent radiation.

Inclusion Criteria

I am either before or after menopause.

My breast cancer cannot be removed by surgery or cured with radiation.

My tumor is positive for estrogen or progesterone receptors and negative for HER2.

Exclusion Criteria

You are allergic to palbociclib, fulvestrant, or goserelin.

I haven't had major cancer treatment or surgery in the last 2 weeks.

I have not had a severe heart problem in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fulvestrant with palbociclib until disease progression or unacceptable toxicity

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Palbociclib

Trial Overview The study tests the effectiveness of continuing palbociclib alongside fulvestrant after initial progression on palbociclib with an aromatase inhibitor. It aims to understand if this combination can further help control the disease.

How Is the Trial Designed?

Group I: Palbociclib and Fulvestrant Experimental Treatment 2 Interventions

Participants will receive fulvestrant with palbociclib until disease progression or unacceptable toxicity.

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

Approved in United States as Ibrance for:

• HR-positive, HER2-negative advanced or metastatic breast cancer

Approved in European Union as Ibrance for:

• HR-positive, HER2-negative locally advanced or metastatic breast cancer

Approved in Canada as Ibrance for:

• HR-positive, HER2-negative advanced or metastatic breast cancer

Approved in Japan as Ibrance for:

• HR-positive, HER2-negative advanced or recurrent breast cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

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]

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]

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]

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 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]

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 phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., 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]

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. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625004655

metastatic breast cancer: A Flatiron Health database analysis However, a few studies have found palbociclib dose reductions to be associated with longer rwPFS or overall survival (OS), but in some instances the impact was ...

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5061543/

Palbociclib in Combination With Fulvestrant in Women ... Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic ...

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

Final Overall Survival in the Phase III FALCON Trial In 2016, FALCON met its primary end point, demonstrating significant improvement in progression-free survival (PFS) with fulvestrant 500 mg ...

8. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07790-z

Real-world safety of palbociclib in breast cancer patients in ... This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia.