Neoadjuvant Palbociclib + Endocrine Therapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Diana M Gibson

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Nebraska

Must be taking: Palbociclib, Letrozole, Goserelin

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Metastatic disease, Liver disease, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) breast cancer do not achieve good responses with pre-operative chemotherapy. The sensitivity of breast cancer to chemotherapy is often determined by the underlying gene expression pattern and the molecular subtype of the tumor. In addition, not all patients tolerate chemotherapy well. Pre-operative endocrine therapy has emerged as an effective strategy to improve outcomes in patients with early-stage hormone receptor positive breast cancer. This study will assess the role of neo-adjuvant palbociclib (CDK 4/6 inhibitor) in combination with letrozole (aromatase inhibitor) +/-Goserelin (GnRH analogue) to improve overall response and surgical feasibility in post and pre-menopausal hormone receptor positive and Her-2 negative subjects with stage IIA-IIIC breast cancer.

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

The trial requires that you do not take any medications that are strong inhibitors or inducers of CYP3A enzymes within 7 days before joining. If you are on exogenous hormone therapy, you will need to stop, except for topical vaginal estrogen therapy, which is allowed.

What data supports the effectiveness of the drug Palbociclib (Ibrance) in combination with endocrine therapy for breast cancer?

Palbociclib, when combined with endocrine therapy like letrozole or fulvestrant, has been shown to significantly extend the time patients live without their cancer getting worse in cases of advanced breast cancer. This combination has been effective in improving outcomes for patients with hormone receptor-positive, HER2-negative breast cancer. ^{1 2 3 4 5}

Is Palbociclib safe for humans?

Palbociclib, also known as Ibrance, has been shown to be generally safe for humans when used in combination with other treatments for certain types of breast cancer. The most common side effect is neutropenia (a low level of white blood cells), but it is usually manageable and not often linked to serious infections. ^{1 2 4 6 7}

How is the drug Palbociclib unique in treating breast cancer?

Palbociclib is unique because it is an oral drug that specifically targets and inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), which are crucial for cancer cell growth. When combined with endocrine therapy, it enhances the effectiveness of hormone treatments like letrozole and fulvestrant, offering a new approach for patients with hormone receptor-positive, HER2-negative breast cancer. ^{1 2 4 8 9}

Research Team

Jairam Krishnamurthy, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for adults at least 19 years old with advanced stage ER+ and/or PR+, HER2- breast cancer, who can take oral medication and have normal organ function. It's not for those previously treated with CDK inhibitors, allergic to similar compounds, with significant liver disease or absorption issues, unstable heart conditions, pregnant/breastfeeding women, HIV-positive on antiretrovirals, men, those with known metastasis or taking certain other drugs.

Inclusion Criteria

My breast cancer is ER+/PR+, HER2-, and either larger than 2 cm or smaller with lymph node involvement.

I can take care of myself and am up and about more than half of the day.

I am 19 years old or older.

Exclusion Criteria

Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.

Currently receiving any other investigational agents.

I do not have any conditions that affect how my body absorbs medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant palbociclib in combination with letrozole +/- Goserelin for six cycles

6 months

Monthly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Palbociclib

Trial Overview The study tests Palbociclib (a CDK inhibitor) combined with letrozole (an aromatase inhibitor) +/- Goserelin (GnRH analogue), as a pre-surgery treatment to improve responses in hormone receptor positive breast cancer patients. The goal is better surgical outcomes without chemotherapy.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

The following drugs will be taken for six cycles: Palbociclib at a dose of 125 mg should be taken by mouth with food on 21 days and 7 days off schedule (meaning: on Days 1-21 of each 28-day cycle). Letrozole should be taken daily by mouth, every day of each 28-day cycle, at a dose of 2.5 mg. Goserelin is given as subcutaneous injection every 28 days at a dose of 3.6 mg. It is to be given on Day 1 of each cycle. Goserelin will only be administered to pre-menopausal subjects.

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?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Jairam Krishnamurthy

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

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 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 a selective inhibitor of CDK4 and CDK6, which are crucial for cell cycle regulation, and has been approved in the US for use with letrozole as a first-line treatment for advanced breast cancer in postmenopausal women.

Ongoing clinical trials are exploring palbociclib's efficacy in various cancer types, including non-small cell lung cancer and other solid tumors, indicating its potential as a versatile treatment option in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: first global approval. Dhillon, S.[2018]

Everolimus, when combined with the aromatase inhibitor exemestane, improved progression-free survival in patients with hormone receptor-positive advanced breast cancer, although it did not affect overall survival.

The CDK4/6 inhibitor palbociclib, used with letrozole or fulvestrant, significantly increased progression-free survival compared to endocrine therapy alone, marking a significant advancement in treatment options for ER+ve/HER2-ve advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer. Boér, K.[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 of 517 patients with hormone receptor-positive metastatic breast cancer, palbociclib combined with fulvestrant was found to be well-tolerated, with neutropenia being the most common adverse effect, occurring in 55% of patients as grade 3 and 10% as grade 4.

Despite the occurrence of neutropenia, dose modifications were effective in managing this side effect without negatively impacting progression-free survival, indicating that palbociclib can be safely integrated into treatment regimens for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3). Verma, S., Bartlett, CH., Schnell, P., et al.[2022]

Palbociclib, a selective CDK4/6 inhibitor, has been shown to be effective when combined with letrozole or fulvestrant in treating HR+/HER2- advanced breast cancer, particularly in cases where patients have developed resistance to standard endocrine therapies.

The combination of palbociclib with endocrine therapy is well tolerated by patients, making it a valuable addition to treatment options for locally advanced and metastatic ER+/HER2- breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Palbociclib combinations as new therapeutic strategies in the treatment of HR+/HER2- advanced breast cancer]. Boér, K.[2019]

In a phase III trial involving 601 patients with aromatase inhibitor-resistant metastatic breast cancer, palbociclib combined with endocrine therapy did not show superior progression-free survival compared to capecitabine, with median PFS of 7.5 months versus 10.0 months in the second cohort.

However, palbociclib plus endocrine therapy had a better safety profile, with fewer severe side effects and improved quality of life for patients compared to capecitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL. Martin, M., Zielinski, C., Ruiz-Borrego, M., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]

3. England 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. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Palbociclib: first global approval. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3). [2022]

8. Hungary pubmed.ncbi.nlm.nih.gov

[Palbociclib combinations as new therapeutic strategies in the treatment of HR+/HER2- advanced breast cancer]. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL. [2022]