Neoadjuvant Palbociclib + Endocrine Therapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Rubayat I Khan

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for certain types of early-stage breast cancer. The researchers aim to determine if adding palbociclib (also known as Ibrance, a type of targeted cancer therapy) to hormone treatments like letrozole can improve surgical outcomes for patients with hormone receptor-positive and HER2-negative breast cancer. This trial may suit individuals with stage IIA-IIIC breast cancer driven by hormones who are not currently on hormone therapy. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

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.

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

Research has shown that palbociclib, a medication used in this trial, is generally well-tolerated. A previous study found no new safety issues, and only about 9.7% of participants stopped taking it due to side effects. This indicates that most people can take the treatment without major problems. Additionally, palbociclib is already approved for other uses, confirming its safety.

The study also includes letrozole and goserelin. Letrozole reduces estrogen levels, while goserelin is a hormone therapy. These treatments are commonly used for hormone-positive breast cancer and have well-established safety records. Overall, most patients can manage the combination of these treatments in the trial. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Palbociclib with endocrine therapy for breast cancer because it offers a novel approach compared to standard treatments. Unlike traditional options that primarily rely on surgery or chemotherapy, Palbociclib is a targeted therapy that specifically inhibits CDK4/6 proteins, which are crucial for cancer cell division. This mechanism not only targets cancer cells more precisely but also has the potential to reduce side effects associated with broader treatments. Additionally, the combination with endocrine therapies, Letrozole and Goserelin, aims to enhance the overall effectiveness, particularly in pre-menopausal women, by further blocking hormone receptors that fuel cancer growth.

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

Research has shown that palbociclib, when combined with hormone therapy like letrozole, holds promise for treating hormone receptor-positive breast cancer. One study found that 85% of patients responded to this combination treatment, with cancer becoming undetectable in 40% of these cases. Another study revealed that when patients took palbociclib with an aromatase inhibitor (such as letrozole), 88% did not experience cancer progression over a year. Palbociclib blocks certain proteins that aid cancer cell growth, making it a targeted treatment option. These findings suggest that palbociclib can effectively manage this type of breast cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Amulya Yellala, MBBS

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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]

Citations

1. onclive.com onclive.com/view/neoadjuvant-palbociclib-plus-endocrine-therapy-does-not-improve-pepi-scores-in-resectable-hr-breast-cancer

Neoadjuvant Palbociclib Plus Endocrine Therapy Does Not ... Clinical Outcomes and Safety. Findings also showed that the clinical response rate was 55.6% in the palbociclib arm vs 44.9% in the placebo arm.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5763422/

Neoadjuvant palbociclib on ER+ breast cancer (N007) The clinical response rate was 85%, with 40% being complete response. The ultrasound response rate was 70%, which was higher than the expected of 50%. All ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6330732/

Real-World Effectiveness of Palbociclib Versus Clinical ... This study suggests that there is no efficacy-effectiveness gap for palbociclib in the treatment of HR-positive, HER2-negative advanced or metastatic breast ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0149291822003794

Real-world Treatment Patterns and Clinical Outcomes ... The 12-month progression-free rate was 88% for palbociclib plus an AI and 79% for palbociclib plus fulvestrant; the 12-month survival rate was 96% in both ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00121-8/abstract

Final survival results from the PENELOPE-B trial ... After a median follow-up of 77.8 months, we recorded 225 deaths (108 palbociclib; 117 placebo) with a 6-year overall survival (OS) rate of 82.4% ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12433830/

Neoadjuvant palbociclib in women with operable, hormone ... No new safety signals were reported. Permanent treatment discontinuation by adverse events was reported for seven (9.7%) and zero patients in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05069038

Study Details | NCT05069038 | Clinical Trial Assessing the ... This study will assess the role of neo-adjuvant palbociclib (CDK 4/6 inhibitor) in combination with letrozole (aromatase inhibitor) +/-Goserelin (GnRH analogue) ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922000351

Survival outcomes after neoadjuvant letrozole and ... Seven deaths have occurred until data cutoff; six in the letrozole-palbociclib arm (two from breast cancer and four unrelated: 1 from endometrial cancer, 1 from ...

9. esmoopen.com esmoopen.com/article/S2059-7029(24)01235-3/fulltext

Palbociclib combined with endocrine treatment in hormone ... The safety profile seems favorable and in contrast to chemotherapy palbociclib does not impact OF throughout the treatment period. Key words.