- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
May 8, 2023 updated by: Washington University School of Medicine
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).
Study Overview
Status
Recruiting
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
81
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Douglas Adkins, M.D.
- Phone Number: 314-747-8475
- Email: dadkins@wustl.edu
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Contact:
- Douglas Adkins, M.D.
- Phone Number: 314-747-8475
- Email: dadkins@wustl.edu
-
Principal Investigator:
- Douglas Adkins, M.D.
-
Sub-Investigator:
- Peter Oppelt, M.D.
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Sub-Investigator:
- Esther Lu, Ph.D.
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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 30 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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1: Palbociclib + Cetuximab
|
Administered on an outpatient basis
Other Names:
Given intravenously over approximately 60 minutes
Other Names:
|
Active Comparator: Arm 2: Cetuximab
-Cetuximab: Initial dose 400mg/m^2 intravenous (IV); Subsequent doses 250 mg/m^2 IV, weekly
|
Given intravenously over approximately 60 minutes
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Through completion of follow-up (estimated to be 15 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR) - (complete response + partial response)
Time Frame: Through completion of treatment (estimated to be 12 weeks)
|
|
Through completion of treatment (estimated to be 12 weeks)
|
Duration of response (DoR)
Time Frame: Through completion of treatment (estimated to be 12 weeks)
|
-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).
|
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)
|
|
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)
|
-Will be measured by CTCAE v. 5.0
|
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)
|
Through completion of treatment (estimated to be 12 weeks)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Douglas Adkins, M.D., Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 6, 2022
Primary Completion (Anticipated)
February 28, 2027
Study Completion (Anticipated)
February 28, 2027
Study Registration Dates
First Submitted
July 7, 2021
First Submitted That Met QC Criteria
July 7, 2021
First Posted (Actual)
July 19, 2021
Study Record Updates
Last Update Posted (Actual)
May 9, 2023
Last Update Submitted That Met QC Criteria
May 8, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Head and Neck Neoplasms
- Neoplasms, Squamous Cell
- Disease Progression
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Palbociclib
- Cetuximab
Other Study ID Numbers
- 202108203
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HPV-unrelated Head and Neck Squamous Cell Carcinoma
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Ezra CohenThe V Foundation for Cancer ResearchRecruitingHead and Neck Cancer | HPV-Related Malignancy | Head and Neck Squamous Cell Carcinoma | Head and Neck Carcinoma | HPV-Related Carcinoma | HPV-Related Squamous Cell Carcinoma | Head and Neck Cancer Stage IV | Head and Neck Cancer Stage IIIUnited States
-
Cue BiopharmaMerck Sharp & Dohme LLCActive, not recruitingHead and Neck Cancer | HPV-Related Carcinoma | HPV Positive Oropharyngeal Squamous Cell CarcinomaUnited States
-
University of ChicagoRecruitingHead and Neck Cancer | HPV Positive Oropharyngeal Squamous Cell Carcinoma | HPV | Human Papilloma VirusUnited States
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Icahn School of Medicine at Mount SinaiWithdrawnHuman Papillomavirus (HPV) | Head and Neck Squamous Cell Carcinoma (HNSCC)United States
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Dan ZandbergMerck Sharp & Dohme LLC; ISA PharmaceuticalsRecruitingHead and Neck Squamous Cell Carcinoma | HPV-Related Squamous Cell CarcinomaUnited States
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Andrew SikoraAdvaxis, Inc.CompletedHead and Neck Cancer | Squamous Cell Carcinoma of the Head and Neck | HPV Positive Oropharyngeal Squamous Cell CarcinomaUnited States
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Dana-Farber Cancer InstituteActive, not recruitingOropharyngeal Squamous Cell Carcinoma | HPVUnited States
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University of California, IrvineRecruitingHPV Positive Oropharyngeal Squamous Cell CarcinomaUnited States
-
University of EdinburghRecruitingOropharyngeal Squamous Cell Carcinoma | Human Papillomavirus (HPV)United Kingdom
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