Palbociclib + Endocrine Therapy for Breast Cancer

Not currently recruiting at 10 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: LHRH agonists

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Stage IV cancer, Uncontrolled illness, HIV, 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: 1

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores breast cancer's response to treatment before surgery using a combination of endocrine therapy and the drug Palbociclib, compared to endocrine therapy alone. The focus is on hormone receptor-positive breast cancer, which grows in response to hormones. Different treatment paths involve combining Palbociclib with therapies like Letrozole or Tamoxifen. Women with hormone receptor-positive, HER2-negative breast cancer and a tumor size of at least 1.5 cm may qualify for this study. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take medications that strongly affect certain liver enzymes (CYP3A) within 7 days of starting the trial. Hormonal contraceptives and hormone replacement therapies are also not allowed.

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

Studies have shown that palbociclib, when combined with hormone therapy, maintains a consistent and stable safety record. It has been used safely for patients with hormone receptor-positive breast cancer. A long-term study over five years supports this, showing it is well-tolerated.

Real-world data from countries like the UK, Spain, and Germany confirm these findings. They demonstrate that palbociclib plus hormone therapy is effective and safe. In some studies, about 15% of patients started with a lower dose, which was managed without major issues.

Letrozole and tamoxifen are also part of the treatments. Both are well-known hormone therapies used in breast cancer treatment. They have been around for a long time and are generally considered safe. These treatments have been widely tested and used, providing a good understanding of their safety.

While specific data on letrozole and tamoxifen in this context isn't detailed here, their long-standing use in breast cancer treatment suggests a reliable safety record. Overall, the treatments in this trial are supported by existing safety evidence, making them promising options for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine endocrine therapy with Palbociclib, a targeted therapy that inhibits cancer cell division. While standard care for hormone receptor-positive breast cancer often involves endocrine therapy alone, adding Palbociclib could enhance effectiveness by directly interrupting cancer cell growth. This dual approach has the potential to improve outcomes by not only blocking the hormones that fuel breast cancer but also by directly targeting the cancer cell cycle. By combining these mechanisms, these treatments may offer a more comprehensive attack on breast cancer cells.

What evidence suggests that this trial's treatments could be effective for Hormone Receptor Positive Breast Cancer?

Research shows that palbociclib, when combined with hormone therapy, effectively treats hormone receptor-positive breast cancer. One study found that this combination can reduce the risk of cancer progression by 30%. Real-world evidence from the UK, Spain, and Germany also supports its effectiveness for advanced stages of this cancer. In this trial, some participants will receive Letrozole followed by endocrine therapy, while others will receive Tamoxifen followed by endocrine therapy. Certain trial arms will combine Letrozole or Tamoxifen with Palbociclib during the endocrine therapy phase. Letrozole and Tamoxifen are well-known hormone therapies that slow or stop cancer growth by blocking hormones like estrogen. Together, these treatments offer promising options for managing hormone receptor-positive breast cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Otto Metzger, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with hormone receptor positive, HER2 negative invasive breast cancer that hasn't spread beyond Stage III. Participants must have a tumor size of at least 1.5 cm and be able to take oral medication. Men, pregnant women, those with certain other cancers or illnesses, and anyone who has had prior CDK inhibitor treatment or endocrine therapy within the last five years cannot join.

Inclusion Criteria

My HER2 test results are unclear.

I am taking medication for bone thinning while on this study.

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

Exclusion Criteria

My breast cancer is not Stage IV.

Concurrent therapy with other Investigational Products

You have had allergic reactions to drugs similar to palbociclib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Window Treatment

Participants receive a two-week course of tamoxifen or letrozole to evaluate anti-proliferative activity

2 weeks

1 visit (in-person)

Treatment

Participants receive endocrine therapy with or without palbociclib for a total duration of 24 weeks

24 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole
• Palbociclib
• Tamoxifen

Trial Overview The PELOPS study is testing how well breast cancer responds to preoperative endocrine therapy alone versus in combination with Palbociclib. It's designed to compare the effectiveness of these treatments in shrinking tumors before surgery in patients with hormone receptor positive breast cancer.

How Is the Trial Designed?

Group I: Tamoxifen Followed By Endocrine Therapy and Palbociclib Experimental Treatment 3 Interventions

Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks.

Group II: Letrozole Followed By Endocrine Therapy and Palbociclib Experimental Treatment 3 Interventions

Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks.

Group III: Arm B Letrozole Followed By Endocrine Therapy Experimental Treatment 2 Interventions

Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks.

Group IV: Arm A Tamoxifen followed by Endocrine Therapy Experimental Treatment 2 Interventions

Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks.

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

Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

In a study with a median follow-up of about 38 months, palbociclib combined with letrozole significantly improved progression-free survival (PFS) in women with advanced estrogen receptor-positive (ER+)/HER2-negative breast cancer, with a median PFS of 27.6 months compared to 14.5 months for the placebo group.

The treatment not only prolonged PFS but also delayed the need for chemotherapy and maintained a favorable safety profile and quality of life for patients, suggesting that palbociclib-letrozole should be the standard first-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Rugo, HS., Finn, RS., Diéras, V., et al.[2023]

Palbociclib, an inhibitor of CDK4 and CDK6, was granted accelerated FDA approval for treating advanced breast cancer in postmenopausal women when combined with letrozole, based on a trial involving 165 patients that showed significant improvement in progression-free survival (PFS).

The trial demonstrated a nearly 50% reduction in the risk of disease progression for patients receiving the combination therapy compared to those on letrozole alone, although the most common side effect noted was neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Beaver, JA., Amiri-Kordestani, L., Charlab, R., 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]

Tamoxifen is the standard treatment for postmenopausal women with hormone-sensitive early breast cancer, but it has side effects that have led researchers to look for safer alternatives.

Third-generation aromatase inhibitors like anastrozole, letrozole, and exemestane have shown better efficacy and a more favorable side effect profile compared to tamoxifen in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. Grana, G.[2018]

Palbociclib, in combination with letrozole, is FDA-approved for treating postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer, showing its efficacy as an initial therapy.

The combination of palbociclib with fulvestrant has been found to provide better outcomes than fulvestrant alone for patients who have previously progressed on endocrine therapy, highlighting its potential in advanced treatment scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. Lu, J.[2022]

In the PALOMA-2 trial, palbociclib combined with letrozole significantly improved progression-free survival (PFS) in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer, with a median PFS of 37.2 months compared to 27.4 months for the placebo group.

The study found that 44% of patients on palbociclib achieved an objective response, and even those who did not achieve a response still experienced a significant prolongation of PFS, indicating that palbociclib + letrozole offers substantial clinical benefits regardless of the response status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2. Rugo, HS., Finn, RS., Gelmon, K., et al.[2021]

In a randomized trial, letrozole significantly improved disease-free survival by 19% and reduced the risk of breast cancer recurrence by 28% compared to tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer.

Letrozole is considered cost-effective, providing an additional 0.343 quality-adjusted life years (QALYs) at an incremental cost of Can$ 8,110, resulting in a cost per QALY gained of Can$ 23,662 from the Canadian healthcare perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in postmenopausal women with hormone-receptor positive early breast cancer from a Canadian perspective. Delea, TE., El-Ouagari, K., Karnon, J., 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 the phase II PALOMA-1/TRIO-18 trial involving 165 postmenopausal women with advanced ER-positive, HER2-negative breast cancer, palbociclib combined with letrozole significantly improved progression-free survival (PFS) to 20.2 months compared to 10.2 months with letrozole alone, indicating its efficacy as a first-line treatment.

While Grade 3-4 neutropenia was the most common adverse event associated with the palbociclib and letrozole combination, the incidence of neutropenia decreased over time, and most patients did not experience severe infections, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. Finn, RS., Crown, JP., Ettl, J., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9553912/

Real-world study of overall survival with palbociclib plus ... The 5-year survival rate for de novo MBC is only 29.0%. The majority (68%) of breast cancer cases have a hormone receptor–positive (HR+)/human ...

2. onclive.com onclive.com/view/real-world-outcomes-support-use-of-first-line-palbociclib-plus-et-in-hr-her2-advanced-breast-cancer

Real-World Outcomes Support Use of First-Line Palbociclib ... Real-world data from the UK, Spain, and Germany support palbociclib plus endocrine therapy as effective for HR-positive/HER2-negative advanced ...

3. nature.com nature.com/articles/s41523-025-00786-z

Real-world effectiveness of palbociclib plus an aromatase ... In a large (n = 2888), heterogeneous population in the United States, palbociclib plus ET was associated with a 30% reduction in risk of disease ...

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

Real-world effectiveness of palbociclib plus endocrine therapy ... Together with prior clinical trial and real-world data, this study helps support the use of palbociclib + ET for patients with HR+/HER2– ABC.

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

metastatic breast cancer: A Flatiron Health database analysis In the current study, approximately 15 % of patients treated with palbociclib had a reduced starting dose (100/75 mg/day); per protocols, this did not occur in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8100571/

Long‐Term Pooled Safety Analysis of Palbociclib in ... This 5-year, long-term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/ ...

7. nature.com nature.com/articles/s41523-022-00479-x

Real-world study of overall survival with palbociclib plus ... Progression-free survival (95% CI) is 19.3 (17.5–20.7) versus 13.9 (12.5–15.2) months, respectively (hazard ratio, 0.70 [95% CI, 0.62–0.78]; P < ...

8. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-announces-overall-survival-results-phase-3-paloma-2

Pfizer Announces Overall Survival Results from Phase 3 ... The results demonstrated IBRANCE plus letrozole resulted in an improved median PFS of 24.8 months when compared to 14.5 months with placebo plus letrozole.