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

NCT ID: NCT04966481

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-06
• Study Completion Date: 2028-02-28

Brief Summary

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

HPV-unrelated Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Palbociclib + Cetuximab

• Palbociclib by mouth 125 mg/daily on Days 1-21 of each 28 day cycle
• Cetuximab: Initial dose 400mg/m^2 intravenous (IV); Subsequent doses 250 mg/m^2 IV, weekly

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

Administered on an outpatient basis

Cetuximab

Intervention Type: DRUG

Given intravenously over approximately 60 minutes

Arm 2: Cetuximab

-Cetuximab: Initial dose 400mg/m\^2 intravenous (IV); Subsequent doses 250 mg/m\^2 IV, weekly

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: DRUG

Given intravenously over approximately 60 minutes

Interventions

Palbociclib

Administered on an outpatient basis

Intervention Type: DRUG

Cetuximab

Given intravenously over approximately 60 minutes

Intervention Type: DRUG

Other Intervention Names

Ibrance; Erbitux

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed RM-HNSCC that is HPV-unrelated disease; defined as SCC of the oral cavity, larynx, or hypopharynx and p16 negative SCC of the oropharynx or p16 negative non-cutaneous SCC unknown primary of the neck.
• CDKN2A loss-of-function (LOF) alteration: mutation or homozygous deletion described on genomic sequencing report.
• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam, per RECIST 1.1.
• Disease progression on a PD-1/L1 inhibitor-containing regimen (given as monotherapy or in combination with other therapy).
• Received no more than three lines of prior therapy for RM-HNSCC.
• At least 18 years of age.
• ECOG performance status ≤ 1.
• Normal bone marrow and organ function as defined below:

• Hemoglobin ≥ 8 g/L
• Absolute neutrophil count ≥ 1,000/mcl
• Platelets ≥ 100,000/mcl
• Total bilirubin ≤ 3 x institutional upper limit of normal (IULN)
• AST(SGOT)/ALT(SGPT) ≤ 5 x IULN (for cases involving liver metastases, AST/ALT ≤ 10 x IULN)
• Serum creatinine < 3 x IULN or creatinine clearance > 30 mL/min by Cockcroft-Gault
• The effects of palbociclib and cetuximab on the developing human fetus are unknown. For this reason and because CDK 4/6 inhibitors are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 3 months days after completion of the study
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria

• Prior treatment with cetuximab for recurrent or metastatic disease (however, prior cetuximab given as a component of multimodality therapy for newly diagnosed, locally advanced, non-metastatic HNSCC is allowable).
• Prior treatment with a CDK4/6 inhibitor for RM-HNSCC.
• Rb (retinoblastoma) loss: mutation or homozygous deletion described on genomic sequencing report.
• Currently receiving any other investigational agents.
• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 1 year before registration and the patient has no evidence of recurrent/persistent disease.
• Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or other agents used in the study (excluding cetuximab).
• Prior grade 3 or 4 (per CTCAE 5.0) hypersensitivity reaction to cetuximab.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• QTc >500 msec (using Bazette formula).
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended. Recommend exclusion of specific ART agents based on predicted drug-drug interactions (i.e. for sensitive CYP3A4 substrates, concurrent strong CYP3A4 inhibitors (ritonavir and cobicistat) or inducers (efavirenz) should be contraindicated).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

The Joseph Sanchez Foundation

UNKNOWN

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Douglas Adkins, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Saint Luke's Hospital

Kansas City, Missouri, United States

Site Status: RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status: RECRUITING

Sanford Medical Center

Sioux Falls, South Dakota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Douglas Adkins, M.D.

Role: CONTACT

dadkins@wustl.edu

314-747-8475

Facility Contacts

Timothy Pluard, M.D.

Role: primary

816-932-3300

Douglas Adkins, M.D.

Role: primary

dadkins@wustl.edu

314-747-8475

Daniel Almquist, M.D.

Role: primary

701-234-6161

Steven Powell, M.D.

Role: primary

605-328-8000

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

202108203

Identifier Type: -

Identifier Source: org_study_id