Actively Recruiting

Phase 3
Age: 18Years +
All Genders
NCT04966481

Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1/L1 Inhibitor

Led by Washington University School of Medicine · Updated on 2026-04-20

81

Participants Needed

5

Research Sites

307 weeks

Total Duration

On this page

Sponsors

W

Washington University School of Medicine

Lead Sponsor

P

Pfizer

Collaborating Sponsor

AI-Summary

What this Trial Is About

This multicenter, open-label, randomized phase 3 trial will determine if palbociclib and cetuximab (Arm 1) improves overall survival (OS) in comparison to cetuximab monotherapy (Arm 2) in patients with CDKN2A-altered, HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on a PD-1/L1 inhibitor (given as monotherapy or in combination with other therapy).

CONDITIONS

Official Title

Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1/L1 Inhibitor

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Histologically or cytologically confirmed recurrent or metastatic HPV-unrelated head and neck squamous cell carcinoma including SCC of the oral cavity, larynx, hypopharynx, and p16 negative SCC of the oropharynx or non-cutaneous SCC unknown primary of the neck
  • CDKN2A loss-of-function alteration (mutation or homozygous deletion) confirmed by genomic sequencing
  • Measurable disease with lesions �3 10 mm by CT scan, �3 20 mm by chest x-ray, or �3 10 mm by clinical exam per RECIST 1.1
  • Disease progression on a PD-1/L1 inhibitor-containing regimen
  • Received no more than three prior therapies for recurrent or metastatic disease
  • At least 18 years old
  • ECOG performance status of 0 or 1
  • Normal bone marrow and organ function including hemoglobin �3 8 g/L, neutrophils �3 1,000/mcL, platelets �3 100,000/mcL, bilirubin �4 3x institutional upper limit, AST/ALT �4 5x institutional upper limit (or �4 10x if liver metastases), creatinine �3x institutional upper limit or creatinine clearance �30 mL/min
  • Agreement to use adequate contraception during and after the study if of childbearing potential
  • Ability to understand and sign informed consent
Not Eligible

You will not qualify if you...

  • Prior treatment with cetuximab for recurrent or metastatic disease (except prior use in multimodality therapy for newly diagnosed, non-metastatic disease)
  • Prior treatment with a CDK4/6 inhibitor for recurrent or metastatic disease
  • Retinoblastoma (Rb) loss confirmed by genomic sequencing
  • Currently receiving other investigational agents
  • History of other malignancy unless treatment completed at least 1 year prior with no recurrence
  • Untreated or progressing brain metastases; treated brain metastases allowed if stable for at least 4 weeks
  • Allergic reactions to palbociclib or similar agents (excluding cetuximab)
  • Prior grade 3 or 4 hypersensitivity to cetuximab
  • Uncontrolled serious illness including active infection, heart failure, unstable angina, or arrhythmia
  • QTc interval over 500 msec
  • HIV infection with CD4+ count below 350 cells/mcL or recent AIDS-defining infection; recommended exclusion of certain ART drugs due to interactions

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 5 locations

1

Sanford Worthington Medical Center

Worthington, Minnesota, United States, 56187

Not Yet Recruiting

2

Saint Luke's Hospital

Kansas City, Missouri, United States, 64111

Actively Recruiting

3

Washington University School of Medicine

St Louis, Missouri, United States, 63110

Actively Recruiting

4

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States, 58122

Actively Recruiting

5

Sanford Medical Center

Sioux Falls, South Dakota, United States, 57104

Actively Recruiting

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Research Team

D

Douglas Adkins, M.D.

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1/L1 Inhibitor | DecenTrialz