Palbociclib + Bicalutamide for Breast Cancer

Recruiting at 5 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CDK4/6 inhibitors, Anti-androgens

Disqualifiers: Active infection, Heart failure, Hepatitis, others

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

Compensation: Varies

Number of Visits: 11

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to test the safety and effectiveness of the investigational drug, palbociclib with bicalutamide for the treatment of triple negative, androgen receptor positive breast cancer.

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

The trial protocol does not specify if you must stop all current medications, but you should avoid medications that strongly affect CYP3A4, as they can interact with palbociclib. It's best to discuss your current medications with the trial team to see if any changes are needed.

Is the combination of Palbociclib and Bicalutamide safe for humans?

Palbociclib has been studied extensively and is generally considered safe for treating certain types of breast cancer in both men and women, with no new safety concerns identified in recent studies. However, specific safety data for the combination of Palbociclib and Bicalutamide is not available in the provided research. ^{1 2 3 4 5}

What makes the drug Palbociclib unique for breast cancer treatment?

Palbociclib is unique because it is a cyclin-dependent kinase 4 and 6 inhibitor, which specifically targets hormone receptor-positive breast cancer, and is often used in combination with endocrine therapy to enhance its effectiveness. ^{6 7 8 9 10}

What data supports the effectiveness of the drug combination Palbociclib and Bicalutamide for breast cancer?

Palbociclib has been shown to be effective in treating hormone receptor-positive, HER2-negative advanced breast cancer when combined with other drugs like fulvestrant, significantly improving progression-free survival. This suggests that Palbociclib may be beneficial in similar drug combinations for breast cancer treatment. ^{3 6 11 12 13}

Who Is on the Research Team?

Ayca Gucalp, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with AR(+) metastatic breast cancer who haven't been treated with bicalutamide or CDK4/6 inhibitors. Participants must have adequate organ function, not be pregnant, and agree to use contraception. They should have recovered from previous treatments and cannot have active severe illnesses or a history of certain heart conditions.

Inclusion Criteria

My tumor tests positive for androgen receptors.

My brain cancer has not worsened in the last 3 months.

I have never been treated with bicalutamide.

Exclusion Criteria

You are currently taking any experimental cancer drugs.

You have had allergic reactions to drugs similar to palbociclib.

Pregnant women and women who are breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase I Treatment

Dose finding lead-in to establish the recommended phase II doses for the combination of palbociclib and bicalutamide using a standard 3+3 design

Up to 1 year

Every 2 weeks during Cycle #1 and 2, then every 4 weeks

Phase II Treatment

Efficacy evaluation of palbociclib and bicalutamide at the recommended phase II dose

6 months

Radiographic response evaluation every 8 weeks for cycles 1-6, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bicalutamide
• Palbociclib

Trial Overview The study tests the combination of palbociclib (an investigational drug) and bicalutamide in treating triple negative, AR(+) metastatic breast cancer. It aims to determine the safety and effectiveness of this treatment regimen.

How Is the Trial Designed?

Group I: Palbociclib in Combination with Bicalutamide Experimental Treatment 2 Interventions

This is a non-randomized, open-label, phase I/II trial for patients with AR(+) MBC . There will be a dose finding phase I portion of the study to establish the recommended phase II dose (R2PD). This will be followed by a phase II where efficacy is evaluated. Patients with AR(+)ER(-) breast cancer treated on the phase I at the recommended phase II dose will be counted towards the primary endpoint analysis for the phase II study.

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

Approved in European Union as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Casodex for:

• Metastatic prostate cancer

Approved in Japan as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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]

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]

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]

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 a study involving 1,139 men with hormone receptor-positive metastatic breast cancer, treatment with palbociclib plus endocrine therapy resulted in a significantly longer median duration of treatment (8.5 months) compared to endocrine therapy alone (4.3 months).

The combination of palbociclib and endocrine therapy also showed a higher response rate in real-world settings, with 33.3% of patients responding compared to 12.5% in the endocrine therapy group, while maintaining a safety profile consistent with previous findings in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data of Palbociclib in Combination With Endocrine Therapy for the Treatment of Metastatic Breast Cancer in Men. Kraus, AL., Yu-Kite, M., Mardekian, J., et al.[2022]

In a study of 191 patients with metastatic breast cancer receiving palbociclib, the median progression-free survival was 22.8 months for first-line treatment, indicating significant efficacy of the drug in delaying disease progression.

While 47% of patients experienced severe neutropenia, the overall survival rate at 24 months was 74.2% for first-line treatment, suggesting that palbociclib is effective but requires monitoring for potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program. Palmieri, C., Musson, A., Harper-Wynne, C., et al.[2023]

In a phase II study involving 12 patients with HER2+ metastatic breast cancer and brain metastases, palbociclib combined with trastuzumab showed no significant responses, with the best outcome being stable disease in 6 patients and a median progression-free survival of only 2.2 months.

The study found that patients with stable or responding systemic disease had lower circulating tumor DNA (ctDNA) variant allele fractions and fewer alterations compared to a larger cohort, suggesting that ctDNA levels may correlate with disease progression in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Single-arm Study of Palbociclib in Patients With HER2-positive Breast Cancer With Brain Metastases and Analysis of ctDNA in Patients With Active Brain Metastases. Shah, AN., Santa-Maria, CA., Mukhija, D., et al.[2023]

Citations

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. [2022]

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

Real-World Treatment Patterns and Clinical Outcomes in Patients Receiving Palbociclib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer in Argentina: The IRIS Study. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases. [2022]

5. France pubmed.ncbi.nlm.nih.gov

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

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

FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. [2021]

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

Real-World Data of Palbociclib in Combination With Endocrine Therapy for the Treatment of Metastatic Breast Cancer in Men. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Palbociclib and endocrine therapy in heavily pretreated hormone receptor-positive HER2-negative advanced breast cancer: the UK Compassionate Access Programme experience. [2021]

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

A Phase II Single-arm Study of Palbociclib in Patients With HER2-positive Breast Cancer With Brain Metastases and Analysis of ctDNA in Patients With Active Brain Metastases. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer. [2023]

12. France pubmed.ncbi.nlm.nih.gov

Impact of Dose Reduction on Efficacy: Implications of Exposure-Response Analysis of Palbociclib. [2021]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Prognostic role of tumor subtype and germline BRCA mutation in advanced breast cancer patients treated with palbociclib plus endocrine therapy. [2022]