HPV-unrelated Head and Neck Squamous Cell CarcinomaPhase 3NCT04966481
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
A Phase 3 study testing Palbociclib and Cetuximab in people with HPV-unrelated Head and Neck Squamous Cell Carcinoma, run by Washington University School of Medicine at 5 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HPV-unrelated Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Palbociclib and Cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 5 sitesUnited States
- Study dates
- 6 Apr 2022to 28 Feb 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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
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- 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).
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 4 recruiting
- Recruiting
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Daniel Almquist, M.D., 701-234-6161
Daniel Almquist, M.D.
- Withdrawn
Saint Luke's Hospital
Kansas City, Missouri, 64111
- Recruiting
Sanford Medical Center
Sioux Falls, South Dakota, 57104
Steven Powell, M.D., 605-328-8000
Steven Powell, M.D.
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Douglas Adkins, M.D., 314-747-8475, dadkins@wustl.edu
Douglas Adkins, M.D.
- Not yet recruiting
Sanford Worthington Medical Center
Worthington, Minnesota, 56187
Steven Powell, M.D., 507-372-2941
Steven Powell, M.D.
About this study
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: A Multicenter, Open-Label, Randomized Phase 3 Trial
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).
- Being tested
- Palbociclib, Cetuximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalbociclibDrug
Also called Ibrance
Administered on an outpatient basis
CetuximabDrug
Also called Erbitux
Given intravenously over approximately 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
-Defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.
Measured: Through completion of follow-up (estimated to be 15 months)
Secondary outcomes (7)
Overall response rate (ORR) - (complete response + partial response)
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Through completion of treatment (estimated to be 12 weeks)
Duration of response (DoR)
-The duration of response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measured: Through completion of treatment (estimated to be 12 weeks)
Progression-free survival (PFS)
- Defined as the days from the date of treatment start to progression or death. The alive patients without progression are censored at the last follow-up.
- Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. ): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: Through completion of follow-up (estimated to be 15 months)
Frequency of adverse events
-Will be measured by CTCAE v. 5.0
Measured: 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
Measured: Through completion of treatment (estimated to be 12 weeks)
Correlate CCND1 and PIK3CA alterations with efficacy endpoints
Tailored Next Generation Sequencing Report (performed before trial enrollment) will be collected to tabulate additional somatic genomic alterations to be used to correlate with efficacy endpoints.
Measured: Through completion of follow-up (estimated to be 15 months)
Changes in genomic alterations of tumor
Measured: At baseline and at time of progression (estimated to be 15 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2021
- Study start6 Apr 2022
- Primary completion28 Feb 2029 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HPV-unrelated Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 81 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, The Joseph Sanchez Foundation
- Responsible party
- Sponsor
- Investigators
- Douglas Adkins, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04966481
- Sponsor's protocol ID
- 202108203
- Status last verified
- Sep 2026
- First submitted
- 7 Jul 2021
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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: A Multicenter, Open-Label, Randomized Phase 3 Trial
- ClinicalTrials.gov ID
- NCT04966481
- Acronym / sponsor ID
- 202108203
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 81 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Pfizer, The Joseph Sanchez Foundation
- Study start
- 6 Apr 2022 (actual)
- Primary completion
- 28 Feb 2029 (estimated)
- Study completion
- 28 Feb 2029 (estimated)
- First posted
- 19 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Palbociclib + Cetuximab | Experimental | Drug: Palbociclib, Drug: 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 |
| Arm 2: Cetuximab | Active comparator | Drug: Cetuximab-Cetuximab: Initial dose 400mg/m^2 intravenous (IV); Subsequent doses 250 mg/m^2 IV, weekly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PalbociclibAlso: IbranceAdministered on an outpatient basis | Drug | Arm 1: Palbociclib + Cetuximab |
| CetuximabAlso: ErbituxGiven intravenously over approximately 60 minutes | Drug | Arm 1: Palbociclib + Cetuximab, Arm 2: Cetuximab |
Primary outcome
Overall survival (OS)
Time frame: Through completion of follow-up (estimated to be 15 months)
-Defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.
7 secondary outcomes
Overall response rate (ORR) - (complete response + partial response)
Time frame: Through completion of treatment (estimated to be 12 weeks)
Duration of response (DoR)
Time frame: Through completion of treatment (estimated to be 12 weeks)
Progression-free survival (PFS)
Time frame: Through completion of follow-up (estimated to be 15 months)
Frequency of adverse events
Time frame: 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
Time frame: Through completion of treatment (estimated to be 12 weeks)
Correlate CCND1 and PIK3CA alterations with efficacy endpoints
Time frame: Through completion of follow-up (estimated to be 15 months)
Changes in genomic alterations of tumor
Time frame: At baseline and at time of progression (estimated to be 15 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Douglas Adkins, M.D. principal investigator
Washington University School of Medicine
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Palbociclib and Cetuximab in people with HPV-unrelated Head and Neck Squamous Cell Carcinoma, run by Washington University School of Medicine at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Douglas Adkins, M.D. (314-747-8475, dadkins@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: Through completion of follow-up (estimated to be 15 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.