Targeted Therapy for Metastatic Breast Cancer

(PATINA Trial)

Not currently recruiting at 127 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance Foundation Trials, LLC.

Must be taking: Anti-HER2 therapy

Must not be taking: CYP3A inhibitors/inducers, Antiretrovirals

Disqualifiers: Pregnancy, HIV, Liver disease, others

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

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding palbociclib, a targeted therapy, to a treatment plan improves outcomes for individuals with a specific type of metastatic breast cancer that is both hormone receptor-positive and HER2 positive. The study compares two groups: one receives palbociclib with standard therapies, while the other receives only the standard therapies. It seeks participants with metastatic breast cancer that cannot be treated with surgery or radiation and who have completed a specific type of chemotherapy. As a Phase 3 trial, this study serves as the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications that strongly affect CYP3A enzymes within 7 days of starting the trial. It's best to discuss your current medications with the trial team.

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

Research has shown that palbociclib is generally well-tolerated by patients with advanced breast cancer. Studies indicate that patients taking palbociclib experience good survival rates and maintain their quality of life. For instance, one study found that combining palbociclib with letrozole, a type of hormone therapy, resulted in a median survival of 53.9 months. Another review found that palbociclib was effective and well-tolerated in older patients with advanced breast cancer. While some patients required a lower dose, many managed the treatment without major problems. These findings suggest that palbociclib is relatively safe for most people. ^{1 2 3 4 5}

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

Researchers are excited about Palbociclib for metastatic breast cancer because it introduces a unique mechanism of action as a CDK4/6 inhibitor. Unlike standard treatments that primarily target hormone receptors or HER2, Palbociclib specifically disrupts the cancer cell cycle, potentially slowing tumor growth more effectively. When combined with anti-HER2 and endocrine therapies, it offers a multi-pronged approach that might improve outcomes over existing therapies alone. This combination could enhance the effectiveness of current treatments and offer new hope for patients with advanced stages of the disease.

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

In this trial, participants in Arm A will receive palbociclib combined with AntiHER2 Therapy and Endocrine Therapy. Research has shown that palbociclib, when used with hormone therapy, can significantly aid in treating breast cancer. In a large study with 2,888 patients, adding palbociclib reduced the risk of cancer progression by 30%. Another study found that patients taking palbociclib with letrozole lived for nearly 54 months on average, longer than those not taking palbociclib. These findings suggest that palbociclib can effectively improve outcomes in hormone receptor-positive, HER2+ metastatic breast cancer. Participants in Arm B will receive AntiHER2 Therapy and Endocrine Therapy without palbociclib. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with hormone receptor-positive, HER2+ metastatic breast cancer that can't be removed by surgery or treated with radiation. Participants must have confirmed invasive breast cancer and agree to provide tumor tissue samples. It's not suitable for those who don't meet these specific cancer criteria.

Inclusion Criteria

My breast cancer is confirmed to be HER2+, ER+, or PR+ and metastatic.

My breast cancer cannot be removed by surgery or cured with radiation, and it may have spread.

I agree to provide a tissue sample from my cancer for testing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive a minimum of 4 and maximum of 8 cycles of induction treatment with anti-HER2 therapy

12-24 weeks

Randomized Treatment

Participants are randomized to receive either palbociclib with anti-HER2 therapy and endocrine therapy or anti-HER2 therapy with endocrine therapy alone until confirmed disease progression

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Palbociclib

Trial Overview The study tests if adding palbociclib to anti-HER2 therapy and endocrine therapy (like Anastrozole, Fulvestrant) improves outcomes in patients compared to just anti-HER2 therapy plus endocrine treatment alone.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 7 Interventions

Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression

Group II: Arm B Active Control 5 Interventions

AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression

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?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

SOLTI Breast Cancer Research Group

Collaborator

Trials

44

Recruited

8,000+

PrECOG, LLC.

Collaborator

Trials

19

Recruited

8,000+

UNICANCER

Collaborator

Trials

237

Recruited

352,000+

Syneos Health

Collaborator

Trials

181

Recruited

69,600+

GBG Forschungs GmbH

Collaborator

Trials

50

Recruited

47,500+

Breast Cancer Trials, Australia and New Zealand

Collaborator

Trials

7

Recruited

5,200+

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

German Breast Group

Collaborator

Trials

54

Recruited

48,400+

Fondazione Michelangelo

Collaborator

Trials

10

Recruited

2,700+

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 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 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]

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

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]

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 191 patients with metastatic breast cancer receiving palbociclib, the median progression-free survival was 22.8 months for first-line treatment, indicating significant efficacy of the drug in delaying disease progression.

While 47% of patients experienced severe neutropenia, the overall survival rate at 24 months was 74.2% for first-line treatment, suggesting that palbociclib is effective but requires monitoring for potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program. Palmieri, C., Musson, A., Harper-Wynne, C., et al.[2023]

In a study of 396 female patients with hormone receptor positive, HER2-negative metastatic breast cancer receiving CDK4 and 6 inhibitors, the most common adverse events were neutropenia, diarrhea, and fatigue, with varying frequencies depending on the specific drug used.

The study found that while the overall incidence of adverse events was lower than in clinical trials, the rates of dose reductions and treatment holds due to these events were higher, suggesting that clinicians may be actively managing side effects to help patients continue their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. Price, GL., Sudharshan, L., Ryan, P., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12280009/

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 ...

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

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 ...

3. 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 ...

4. 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 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00137

Overall Survival With Palbociclib Plus Letrozole in ... The median OS was 53.9 months (95% CI, 49.8 to 60.8) with palbociclib plus letrozole versus 51.2 months (95% CI, 43.7 to 58.9) with placebo plus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8676999/

Effectiveness and Safety of Palbociclib plus Endocrine ... For the 23 patients who received palbociclib as second-line therapy for metastatic breast cancer, median progression-free survival was 13.3 months (95% CI 4.1– ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38546943/

Palbociclib in Older Patients with Advanced/Metastatic ... In this systematic review, data from RCTs showed that palbociclib was effective, well tolerated, and maintained QoL in older patients with HR+/HER2- a/mBC.