Palbociclib + Endocrine Therapy for Breast Cancer

(PALLAS Trial)

Not currently recruiting at 476 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance Foundation Trials, LLC.

Must be taking: Adjuvant hormonal

Must not be taking: CDK inhibitors, Antiretrovirals

Disqualifiers: Stage I/IV cancer, Chronic liver disease, 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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding the drug palbociclib (Ibrance) to regular hormone therapy can improve outcomes for people with early breast cancer that is hormone receptor-positive (HR+) and HER2-negative (HER2-). Participants will receive either palbociclib with their hormone therapy or just the hormone therapy alone. Eligible participants must have been diagnosed with early-stage breast cancer that is HR+ and HER2- and must have undergone breast surgery for their current cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take medications that strongly affect CYP3A enzymes within 7 days before starting the trial. You also cannot be on antiretroviral therapy or other investigational drugs.

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

Research has shown that palbociclib, when combined with hormone therapy, is generally safe for people. A five-year study found that this combination remained consistently safe over time, allowing most people to take the treatment without unexpected problems.

However, like any medication, palbociclib can cause side effects. Some studies reported that about 15% of patients needed to lower their dose due to these side effects. It's important to weigh these potential effects against the benefits and discuss them with a doctor.

Overall, palbociclib has been safely used in other conditions, supporting its use in treating breast cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Palbociclib combined with standard endocrine therapy for breast cancer because it introduces a novel approach to treatment. Unlike standard endocrine therapies, which focus on blocking hormones that fuel cancer growth, Palbociclib works by inhibiting proteins called CDK4 and CDK6 that are crucial for cancer cell division. This dual action—hormone suppression and cell cycle interruption—can potentially enhance the effectiveness of treatment, offering hope for better outcomes in breast cancer management.

What evidence suggests that this trial's treatments could be effective for early breast cancer?

In this trial, participants in Arm A will receive a combination of palbociclib and standard adjuvant endocrine therapy. Research has shown that combining palbociclib with hormone therapy effectively treats patients with HR-positive/HER2-negative advanced breast cancer. Studies have found that this combination can reduce the risk of cancer progression by 30%. Real-world evidence from various countries also supports that palbociclib with hormone therapy improves outcomes for this breast cancer type. This suggests that adding palbociclib to standard hormone therapy for early-stage HR+/HER2- breast cancer could potentially lead to better results. Participants in Arm B will receive standard adjuvant endocrine therapy alone. ^{2 3 6 7 8}

Who Is on the Research Team?

Erica L. Mayer, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Angela DeMichele, MD

Principal Investigator

University of Pennsylvania

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Michael Gnant, MD

Principal Investigator

ABCSG, Medical University Vienna

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HR+/HER2- early breast cancer (Stage II or III), who have had surgery, can take oral meds, and are on or starting hormone treatment. They must not be pregnant, have normal organ function tests, no history of other cancers, and no severe illnesses that could affect participation.

Inclusion Criteria

Women who can have babies must have a negative pregnancy test within 14 days before starting the trial.

I have completed my initial cancer treatment and my side effects have mostly gone away.

I have had surgery to remove my breast cancer.

Exclusion Criteria

Concurrent therapy with other Investigational Products.

I am currently on hormone therapy, but topical vaginal estrogen is okay.

Uncontrolled intercurrent illness that would limit compliance with study requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive palbociclib in addition to standard adjuvant endocrine therapy for 2 years

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Palbociclib
• Standard Adjuvant Endocrine Therapy

Trial Overview The study is testing if adding palbociclib to standard endocrine therapy after breast cancer surgery improves patient outcomes compared to endocrine therapy alone. It's a Phase III trial where patients are randomly assigned to two groups in an open-label setting.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 1 Intervention

Standard adjuvant endocrine therapy for a duration of at least 5 years.

Group II: Arm A Experimental Treatment 2 Interventions

Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.

Who Is Running the Clinical Trial?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

Austrian Breast & Colorectal Cancer Study Group

Collaborator

Trials

23

Recruited

18,500+

NSABP Foundation Inc

Collaborator

Trials

89

Recruited

140,000+

PrECOG, LLC.

Collaborator

Trials

19

Recruited

8,000+

Breast International Group

Collaborator

Trials

34

Recruited

53,600+

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

In a phase II trial involving 71 patients with HER2-positive advanced breast cancer, the combination of palbociclib and trastuzumab showed promising progression-free survival rates, particularly in estrogen receptor-positive patients, with rates of 42.8% and 46.4% for different cohorts.

The treatment was generally safe, but a high incidence of grade 1-2 (97.7%) and grade 3-4 (84.4%) toxicities was observed, with neutropenia being the most common severe side effect, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial. Ciruelos, E., Villagrasa, P., Pascual, T., 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]

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]

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]

In two phase 3 trials (PALOMA-2 with 267 participants and PALOMA-3 with 240 participants), palbociclib combined with endocrine therapy significantly prolonged progression-free survival in women with advanced hormone receptor-positive breast cancer, with median survival times of 25.4 months versus 13.7 months in PALOMA-2 and 9.9 months versus 3.5 months in PALOMA-3 compared to placebo.

The safety profile of palbociclib was consistent with previous studies, with neutropenia being the most common side effect, and no new safety concerns were identified, indicating it is a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib plus endocrine therapy in North American women with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Gelmon, KA., Cristofanilli, M., Rugo, HS., et al.[2022]

In a phase 2 study of 42 postmenopausal patients with advanced breast cancer, palbociclib combined with letrozole showed a median progression-free survival of 35.7 months, indicating its effectiveness as a first-line treatment.

The treatment was generally well-tolerated, with common side effects including neutropenia and leukopenia, but no significant decline in quality of life was observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib-letrozole as first-line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study. Takahashi, M., Masuda, N., Nishimura, R., et al.[2021]

In a real-world study of 46 patients with HR-positive, HER2-negative advanced breast cancer, palbociclib combined with endocrine therapy showed a median progression-free survival (PFS) of 10.0 months, which is comparable to the 9.5 months reported in the PALOMA-3 clinical trial.

The tolerability of palbociclib was generally good, with neutropenia being the most common severe adverse event, and most side effects managed through dose modifications, indicating that the treatment is both effective and manageable in a clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness of Palbociclib Versus Clinical Trial Results in Patients With Advanced/Metastatic Breast Cancer That Progressed on Previous Endocrine Therapy. Bui, TBV., Burgers, DM., Agterof, MJ., 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.