Palbociclib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Breast cancer, Myeloma, Liposarcoma, 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

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: 5

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how effectively the medication palbociclib works for individuals with specific genetic changes in their cancer. Palbociclib blocks signals that cause cancer cells to multiply, potentially slowing or stopping the disease's spread. The trial seeks patients with specific mutations in the CDK4 or CDK6 genes, excluding those with breast cancer or certain other conditions. Participants should not have previously used similar treatments and must avoid certain medications. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Do I have to stop taking my current medications?

The trial requires that you do not use drugs or foods that are known potent CYP3A4 inhibitors or inducers, or are CYP3A substrates with narrow therapeutic indices. You may need to stop or adjust these specific medications.

Is there any evidence suggesting that palbociclib is likely to be safe for humans?

Research has shown that palbociclib, a treatment for certain cancers, has been studied for its safety. In a study with 444 patients who took palbociclib with letrozole, common side effects included a drop in white blood cells, which can lead to infections. Other studies, including a five-year analysis, have found that it maintains a stable safety profile, suggesting it is generally safe for patients. However, some real-world data showed increased risks of side effects like low white blood cell count and low platelet count. This indicates that while palbociclib is mostly well-tolerated, some people can experience significant side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer, which often involve chemotherapy or radiation, Palbociclib is a targeted therapy that specifically inhibits cyclin-dependent kinases 4 and 6 (CDK4/6). These proteins play a crucial role in cancer cell division. By blocking these kinases, Palbociclib can effectively slow down the growth of cancer cells, potentially offering a more precise treatment with fewer side effects. Researchers are excited because this approach not only offers a novel mechanism of action but also holds the promise of improved efficacy and tolerability compared to traditional cancer therapies.

What evidence suggests that palbociclib might be an effective treatment for cancer?

Research has shown that palbociclib, when combined with hormone therapy, effectively treats certain breast cancers. Studies have found that this combination can reduce the risk of cancer progression by 30% in many patients. This treatment benefits patients with advanced breast cancer that is hormone receptor-positive (HR+) and lacks an excess of the HER2 protein. Real-world data indicate that about 34% of patients respond well when this is their first treatment. These findings suggest that palbociclib could be effective for cancers with specific gene changes, such as CDK4 or CDK6 mutations. Participants in this trial will receive palbociclib as a standalone treatment to further evaluate its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Mark H O'Hara

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with a specific mutation in the CDK4 or CDK6 gene. It's open to those with lymphoma, solid tumors, and other cancers that haven't responded to standard treatments.

Inclusion Criteria

I am not allergic to palbociclib or similar drugs.

My recent ECG showed no significant heart issues.

My cancer has a specific genetic change related to CDK4 or CDK6.

Exclusion Criteria

I have heart issues related to the left side of my heart.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive palbociclib orally once daily on days 1-21 of each 28-day cycle. Cycles repeat in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the trial.

Up to 3 years

Every 2 cycles for the first 26 cycles, then every 3 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 2 years and then every 6 months for 1 year.

3 years

Every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Palbociclib

Trial Overview The study tests Palbociclib (PD-0332991), a kinase inhibitor targeting mutated CDK4/CDK6 genes in cancer cells. The goal is to see if it can stop or slow cancer growth. Participants will also undergo biospecimen collection, biopsies, CT scans, and MRIs.

How Is the Trial Designed?

Group I: Treatment (palbociclib) Experimental Treatment 5 Interventions

Patients receive palbociclib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI and blood sample collection throughout the trial. Patients may also undergo a biopsy on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

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]

Citations

1. 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 ...

2. 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 ...

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 The median time from palbociclib start to a first dose adjustment was 85 days; 25 % of patients experienced a first dose adjustment at a median time of 52 days ...

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

Real-world effectiveness of palbociclib plus endocrine therapy ... Real-world response and clinical benefit rates with palbociclib + ET were 34.0% and 69.4%, respectively, in 1L, and 21.8% and 57.9% in ≥2L.

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/palbociclib-ibrance

Palbociclib (IBRANCE) Safety data was evaluated in 444 patients who received palbociclib plus letrozole. Neutropenia was the most frequently reported adverse reaction ...

7. 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+/ ...

8. ibrance.pfizerpro.com ibrance.pfizerpro.com/clinical-trial/ibr-ai-efficacy-safety

ibr-ai-efficacy-safety Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment ...

9. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07790-z

Real-world safety of palbociclib in breast cancer patients in ... This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia.

10. esmoopen.com esmoopen.com/article/S2059-7029(25)00158-9/fulltext

Palbociclib exposure in relation to efficacy and toxicity ... Population pharmacokinetics of palbociclib and its correlation with clinical efficacy and safety in patients with advanced breast cancer.