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

NCT04966481 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 202108203
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  -Defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.

  Through completion of follow-up (estimated to be 15 months)

Secondary Outcomes (7)

• Overall response rate (ORR) - (complete response + partial response)

  Through completion of treatment (estimated to be 12 weeks)

• Duration of response (DoR)

  Through completion of treatment (estimated to be 12 weeks)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 15 months)

• Frequency of adverse events

  From start of treatment through 30 days after completion of treatment (estimated to be 16 weeks)

• Dose delivery as measured by percent of full doses given over time

  Through completion of treatment (estimated to be 12 weeks)

Study Arms (2)

Arm 1: Palbociclib + Cetuximab

EXPERIMENTAL

* 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

Drug: Palbociclib; Drug: Cetuximab

Arm 2: Cetuximab

ACTIVE COMPARATOR

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

Drug: Cetuximab

Interventions

Palbociclib DRUG

Administered on an outpatient basis

Also known as: Ibrance

Arm 1: Palbociclib + Cetuximab

Cetuximab DRUG

Given intravenously over approximately 60 minutes

Also known as: Erbitux

Arm 1: Palbociclib + Cetuximab; Arm 2: Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Pfizer: collaborator
• The Joseph Sanchez Foundation: collaborator

Study Sites (5)

Sanford Worthington Medical Center

Worthington, Minnesota, 56187, United States

NOT YET RECRUITING

Saint Luke's Hospital

Kansas City, Missouri, 64111, United States

WITHDRAWN

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

RECRUITING

Sanford Medical Center

Sioux Falls, South Dakota, 57104, United States

RECRUITING

Related Links

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

MeSH Terms

Interventions

palbociclib; Cetuximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Douglas Adkins, M.D.

CONTACT

314-747-8475; dadkins@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: These patients will be randomized on a 2:1 basis to Arm 1 (palbociclib + cetuximab, n=54) or Arm 2 (cetuximab alone, n=27). Patients will be stratified at randomization to balance the proportion of patients in each arm with: 1. previous exposure to a platinum agent (cisplatin or carboplatin given to treat recurrent or metastatic disease, or as a component of multimodality therapy for newly diagnosed locally advanced, non-metastatic HNSCC), 2. previous exposure to cetuximab (given as a component of multimodality therapy for newly diagnosed locally advanced, non-metastatic HNSCC).

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 19, 2021
• Study Start: April 6, 2022
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2028
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)