What is the mechanism of action of this treatment?

CDK4/6 inhibitors, such as Palbociclib, function by blocking cyclin-dependent kinases 4 and 6, essential for cell cycle progression from the G1 to S phase, thereby preventing cancer cell proliferation. This targeted approach is crucial for cancer patients as it specifically disrupts the growth of cancer cells while minimizing damage to normal cells. Other common treatments include chemotherapy, which targets rapidly dividing cells, and immunotherapy, which boosts the immune system's ability to fight cancer. These mechanisms are vital as they provide multiple strategies to control and potentially eradicate cancer, improving patient outcomes and survival rates.

What side effects are associated with this type of intervention?

Common treatments for cancer, particularly those involving CDK4/6 inhibitors like Palbociclib, often result in side effects such as neutropenia (low white blood cell count), anemia, fatigue, nausea, and diarrhea. Other targeted therapies and chemotherapies may also cause neuropathy, thrombocytopenia (low platelet count), and gastrointestinal issues. Additionally, some treatments can lead to specific toxicities like hypocalcemia, hypokalemia, and increased liver enzymes. It's important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

Palbociclib is a CDK4/6 inhibitor that has been approved by the FDA for the treatment of certain types of cancer, particularly hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Other similar CDK4/6 inhibitors that have received FDA approval include ribociclib and abemaciclib. These drugs work by inhibiting the activity of cyclin-dependent kinases 4 and 6, which are crucial for cell cycle progression and cancer cell proliferation. Their approval has provided new therapeutic options for patients with specific cancer subtypes, improving outcomes and offering alternatives to traditional chemotherapy.

What other types of research exist?

Promising alternatives to Palbociclib for cancer treatment in 2024 include: 1) Infigratinib and Futibatinib, which are FGFR inhibitors showing efficacy in cholangiocarcinoma with FGFR2 fusions/rearrangements. 2) Pembrolizumab and Nivolumab, immune checkpoint inhibitors that have demonstrated significant benefits in various cancers, including melanoma. 3) Acalabrutinib and Zanubrutinib, BTK inhibitors that are effective in chronic lymphocytic leukemia and mantle cell lymphoma. These therapies offer novel mechanisms of action and have shown promising results in clinical trials.

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CDK4/6 Inhibitor

Palbociclib for Cancer

Phase 2

Waitlist Available

Led By Amy S Clark

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

Patients must have amplification of CCND1, 2, or 3, or another aberration, as determined via the MATCH Master Protocol

Must not have

Patients with known or symptoms of left ventricular dysfunction will be excluded

Patients must not have breast cancer, mantle cell lymphoma or myeloma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Awards & highlights

No Placebo-Only Group

Summary

This trial tests palbociclib, a medication taken by mouth, in patients with advanced cancers that have specific genetic changes. It works by blocking proteins needed for cancer cell growth. Researchers hope it will shrink the cancer or stop it from growing.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Palbociclib may cause side effects like low white blood cell counts (which can lead to increased infection risk), fatigue, nausea, hair thinning or loss, nosebleeds, mouth sores and diarrhea.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My recent ECG showed no significant heart issues.

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

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

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

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I am not allergic to palbociclib or similar drugs.

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I have not been treated with CDK4/6 inhibitors like palbociclib.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR)

Secondary study objectives

6-month Progression-free Survival (PFS) Rate

Progression Free Survival (PFS)

Side effects data

From 2021 Phase 3 trial • 693 Patients • NCT02028507

63%

Neutrophil count decreased

55%

Fatigue

34%

Hypertension

27%

Mucositis

24%

Nausea

22%

Weight gain

20%

Diarrhea

20%

Arthralgia

19%

Upper respiratory infection

19%

Hypothermia

19%

Weight loss

18%

Vomiting

17%

Headache

15%

Anorexia

15%

Back pain

15%

Constipation

15%

Pruritus

14%

Cough

12%

Dyspepsia

12%

Bone pain

11%

Abdominal pain

11%

Fever

10%

Alopecia

10%

Flu like symptoms

10%

Pain

10%

Hot flashes

Dizziness

Obesity

Pain in extremity

Anemia

Dysgeusia

Palmar-plantar erythrodysesthesia syndrome

Nail disorder

Respiratory infection

Catheter related infection

Urinary tract infection

Bone fracture

Stroke

Acidosis

Suicide attempt

Heart failure

Lymphedema

Dyspnea

Pneumonitis

Hip replacement

Tooth infection

Uveitis

Respiratory failure

Febrile neutropenia

Hematoma

Non-cardiac chest pain

Sepsis

Urinary bladder carcinoma

Hypercalcemia

Bacteremia

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Palbociclib Plus Exemestane

Cohort 1 and 2: Capecitabine

Cohort 2: Palbociclib Plus Fulvestrant

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (palbociclib)Experimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Palbociclib

2017

Completed Phase 3

~3880

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

CDK4/6 inhibitors, such as Palbociclib, function by blocking cyclin-dependent kinases 4 and 6, essential for cell cycle progression from the G1 to S phase, thereby preventing cancer cell proliferation. This targeted approach is crucial for cancer patients as it specifically disrupts the growth of cancer cells while minimizing damage to normal cells. Other common treatments include chemotherapy, which targets rapidly dividing cells, and immunotherapy, which boosts the immune system's ability to fight cancer. These mechanisms are vital as they provide multiple strategies to control and potentially eradicate cancer, improving patient outcomes and survival rates.

The role of abemaciclib in treatment of advanced breast cancer.