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

Sponsor

Kathryn Gold (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03498378

Collaborator

Pfizer (Industry)

Enrollment

Location

Arm

60.8

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Carcinoma	Drug: Avelumab Drug: Palbociclib Drug: Cetuximab	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 6, 2018

Actual Primary Completion Date :

Feb 4, 2020

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avelumab, Palbociclib, and Cetuximab Identify the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) for the combination of palbociclib, avelumab, and cetuximab	Drug: Avelumab Avelumab (IV on days 1 and 15 of 28 day cycle) Other Names: Bavencio Drug: Palbociclib 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. Other Names: IBRANCE Drug: Cetuximab 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. Other Names: ERBITUX

Arm

Intervention/Treatment

Experimental: Avelumab, Palbociclib, and Cetuximab

Identify the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) for the combination of palbociclib, avelumab, and cetuximab

Drug: Avelumab

Avelumab (IV on days 1 and 15 of 28 day cycle)

Other Names:

Bavencio

Drug: Palbociclib

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.

Other Names:

IBRANCE

Drug: Cetuximab

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.

Other Names:

ERBITUX

Outcome Measures

Primary Outcome Measures

maximum tolerated dose [12 months]
maximum tolerated dose/recommended phase II dose.

Secondary Outcome Measures

Overall response rate [through study completion, an average of 3 years]
Determined by RECIST 1.1
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] [through study completion, an average of 3 years]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).