Avelumab, Cetuximab, and Palbociclib in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of the study is to find out if the study drugs Avelumab, Cetuximab, and Palbociclib will slow or stop your cancer from getting worse, and whether it causes side effects. The second purpose is to measure whether your cancer responds to the study drugs Avelumab, Cetuximab, and Palbociclib. The study drugs Avelumab, Cetuximab, and Palbociclib are types of drugs called a monoclonal antibody. Monoclonal antibodies are made to recognize, target, and bind to specific proteins on cells the building blocks making up your tissues.

Detailed Description
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This is an open-label phase I trial with a 3+3 dose escalation design. All patients will receive avelumab, cetuximab, and palbociclib. This study will enroll patients with head and neck squamous cell carcinoma not amenable to curative intent therapy. Treatment will be administered in 28 day cycles with a pre-defined dose escalation schedule.

Official Title
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A Phase I Study of Avelumab, Palbociclib, and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Avelumab
* Drug: Palbociclib
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven squamous cell carcinoma of the head and neck not amenable to curative intent therapy. Presence of measurable tumor lesions per RECIST criteria v1.1 Life expectancy greater than 12 weeks. Adequate hematologic, hepatic, and renal function Negative serum or urine pregnancy test for women of child bearing potential Exclusion Criteria: Prior therapy with an EGFR inhibitor or PD-1 or PD-L1 inhibitor in the recurrent or metastatic setting Uncontrolled central nervous system metastases (stable metastases permitted) Chemotherapy 28 days prior to first administration of study treatment and/or monoclonal antibody ≤8 weeks prior to first administration of study treatment. History of other malignancies, Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of >10 mg/day of prednisone or equivalent) Prior organ transplantation Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avelumab, Palbociclib, and Cetuximab<br>Identify the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) for the combination of palbociclib, avelumab, and cetuximab | Drug: Avelumab<br>* Avelumab (IV on days 1 and 15 of 28 day cycle)<br>* Other names: Bavencio;Drug: Palbociclib<br>* Palbociclib (PO daily, days 1-21 of 28 day cycle) Palbociclib will be administered in capsules of 125 mg, 100 mg, and 75 mg, depending on dosage. Patients will be instructed to take their assigned dose once daily with food for 21 days followed by 7 days off therapy. Patients will be encouraged to take their dose at approximately the same time each day.<br>* Other names: IBRANCE;Drug: Cetuximab<br>* Cetuximab (IV 400 mg/m2 x 1, then weekly) Cetuximab is administered intravenously once weekly via infusion pump or syringe pump with infusion rate not to exceed 10 mg/min.<br>* Other names: ERBITUX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose | maximum tolerated dose/recommended phase II dose. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Determined by RECIST 1.1 | through study completion, an average of 3 years | 
| progression free survival |  | through study completion, an average of 3 years | 
| overall survival |  | through study completion, an average of 3 years | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | through study completion, an average of 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, Avelumab, Palbociclib, Cetuximab, Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma