Palbociclib + Endocrine Therapy for Breast Cancer

(PALLAS Trial)

Recruiting at 438 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

5796 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing whether adding the drug palbociclib to standard hormone therapy can improve treatment for patients with a specific type of early breast cancer. The targeted patients have hormone receptor-positive and HER2-negative breast cancer. Palbociclib works by blocking proteins that help cancer cells grow, potentially making the hormone therapy more effective.

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 Palbociclib combined with endocrine therapy safe for humans?

Palbociclib combined with endocrine therapy has been generally well-tolerated in studies, though common side effects include low white blood cell counts (neutropenia and leukopenia) and mouth sores (stomatitis). Serious side effects like fever with low white blood cell count (febrile neutropenia) were rare, and overall, patients did not experience a significant decline in quality of life. ^{1 2 3 4 5}

How is the drug palbociclib plus endocrine therapy unique for breast cancer treatment?

Palbociclib plus endocrine therapy is unique because it combines a cyclin-dependent kinase 4/6 inhibitor with hormone therapy, which helps to significantly prolong progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer compared to hormone therapy alone. ^{3 4 6 7 8}

What data supports the effectiveness of the drug Palbociclib when used with endocrine therapy for breast cancer?

Research shows that adding Palbociclib to endocrine therapy improves progression-free survival (the time during which the cancer does not get worse) in patients with hormone-receptor-positive, HER2-negative metastatic breast cancer. This suggests that Palbociclib can enhance the effectiveness of endocrine therapy in treating certain types of breast cancer. ^{2 7 9 10 11}

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.

My breast cancer is not Stage I or IV.

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 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 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 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. England pubmed.ncbi.nlm.nih.gov

Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. [2022]

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

Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial. [2021]

3. 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]

4. 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]

5. 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]

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

Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. [2023]

7. United States 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. [2022]

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

Palbociclib-letrozole as first-line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study. [2021]

9. United States 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. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of palbociclib plus fulvestrant after everolimus in hormone receptor-positive metastatic breast cancer. [2022]

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

Palbociclib for the Treatment of Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2021]