Palbociclib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CDK4/6 inhibitors

Disqualifiers: Breast cancer, Mantle cell lymphoma, Myeloma, Left ventricular dysfunction, 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 tests a treatment called palbociclib (also known as Ibrance) to determine if it can shrink or stop the growth of certain cancers with specific genetic changes. Palbociclib blocks proteins that aid cancer cell growth. It targets individuals whose cancer exhibits genetic changes known as CCND1, 2, or 3 amplification. Ideal candidates for this trial have these genetic changes and have not previously received palbociclib or similar medications. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 use drugs or foods that strongly affect CYP3A4, an enzyme that processes many medications. It's best to discuss your current medications with the trial team.

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

Research has shown that palbociclib can be a safe treatment option, though it carries some risks. In a study with 444 patients, neutropenia, or a low level of white blood cells, was the most common side effect, increasing the likelihood of infections.

Long-term safety data on palbociclib indicates that its side effects usually remain consistent over time. However, other studies have found that palbociclib can also cause leukopenia (low white blood cells) and thrombocytopenia (low platelets, which help with blood clotting).

Palbociclib is already approved for certain types of breast cancer, providing some reassurance about its safety. However, like all treatments, it's important to weigh the benefits against the risks. Prospective trial participants should discuss potential side effects with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about palbociclib because it offers a novel approach by targeting specific proteins involved in cell division, namely the cyclin-dependent kinases 4 and 6 (CDK4/6). Unlike traditional chemotherapy that attacks rapidly dividing cells indiscriminately, palbociclib selectively inhibits these kinases, potentially leading to fewer side effects and improved outcomes. This targeted action may provide a more tailored and effective treatment option for certain cancers, offering hope for patients whose disease has progressed despite standard therapies.

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

Research has shown that palbociclib can slow cancer cell growth by blocking proteins called CDK4 and CDK6. These proteins are often overly active in cancers with specific genetic changes known as CCND1, 2, or 3 amplifications. In studies with breast cancer patients, when combined with other treatments, palbociclib led to cancer shrinking or halting growth in over half of the patients (55.3%). Additionally, real-world data indicates that this combination can reduce the risk of disease progression by 30%. These findings suggest that palbociclib could be a promising treatment option for cancers with these genetic changes. Participants in this trial will receive palbociclib as the investigational treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Amy S Clark

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients with cancers that have specific genetic changes called CCND1, 2, or 3 amplification. They must not have breast cancer, mantle cell lymphoma or myeloma and should not be on certain drugs affecting heart rhythm. Prior treatment with CDK4/6 inhibitors disqualifies them.

Inclusion Criteria

My recent ECG showed no significant heart issues.

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

My cancer has a specific genetic change related to CCND1, 2, or 3.

Exclusion Criteria

I do not have heart issues related to the left ventricle.

I do not have breast cancer, mantle cell lymphoma, or myeloma.

I am not taking any strong medications or eating foods that affect certain liver enzymes.

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. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

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

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Up to 3 years

Every 3 months for the first 2 years, then every 6 months for year 3

What Are the Treatments Tested in This Trial?

Interventions

• Palbociclib

Trial Overview The trial tests Palbociclib's effectiveness in stopping the growth of cancers with CCND1, 2, or 3 amplifications by blocking proteins CDK4 and CDK6. It's a phase II study to see if this drug can shrink these types of cancers or halt their progression.

How Is the Trial Designed?

Group I: Treatment (palbociclib) Experimental Treatment 1 Intervention

Patients receive palbociclib PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

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]

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]

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]

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 ... Findings supporting the approval showed that patients who received palbociclib plus letrozole (n = 444) experienced an ORR of 55.3% (95% CI, ...

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. 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. 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. ibrance.pfizerpro.com ibrance.pfizerpro.com/

Home Page | IBRANCE® (palbociclib) HCP | Safety Info IBRANCE has been approved with inavolisib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR+/HER2- advanced breast cancer.

8. 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+/ ...

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. dhpp.hpfb-dgpsa.ca dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR1707157428464

Summary Safety Review - Ibrance (palbociclib) Health Canada reviewed 7 randomized controlled trials (RCTs) involving Ibrance, which included 8,793 patients. The majority (>95%) of these patients had early ...