Targeted Therapy for Metastatic Breast Cancer

(PATINA Trial)

Recruiting at 118 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

518 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Palbociclib (Ibrance) for treating metastatic breast cancer?

Research shows that Palbociclib, when combined with another drug called fulvestrant, significantly improved the time patients lived without their cancer getting worse, from about 4.6 months to 9.5 months, compared to those who did not receive Palbociclib. ^{1 2 3 4 5}

Is palbociclib (Ibrance) generally safe for humans?

Palbociclib, also known as Ibrance, has been studied for safety in treating metastatic breast cancer, showing that it can be safely used in combination with other therapies. It has been approved by the FDA for both men and women, with safety data supported by clinical trials and real-world studies. ^{4 6 7 8 9}

How is the drug Palbociclib unique in treating metastatic breast cancer?

Palbociclib is unique because it is an oral drug that specifically targets and inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), which are proteins that help cancer cells grow. This makes it different from traditional chemotherapy, as it works by stopping cancer cell division and is often used in combination with other hormone therapies to enhance their effectiveness. ^{1 3 4 10 11}

What is the purpose of this trial?

The primary objective of this study is to demonstrate that the combination of palbociclib with anti-HER2 therapy plus endocrine therapy is superior to anti-HER2-based therapy plus endocrine therapy alone in improving the outcomes of subjects with hormone receptor-positive, HER2+ metastatic breast cancer.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. 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]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Palbociclib: first global approval. [2018]

4. England 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. [2023]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study. [2021]

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

FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. [2021]

8. England 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. [2022]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]

11. France pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. [2022]