A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy Followed By Standard Chemoradiation In HPV-Negative Locally Advanced Stage III/IVa/IVb HNSCC.
This is a phase I/phase II prospective multicenter trial to investigate the efficacy and
safety of afatinib with induction chemotherapy in primary unresected patients with
HPV-negative locally advanced SCC stage III or IVa/b of oral cavity, oropharynx,
hypopharynx, or larynx. The primary endpoint is overall response rate after the completion
of induction chemotherapy.
Eligible patients will begin with a 14 day lead-in period with afatinib alone. This will be
followed immediately by 2 cycles of induction chemotherapy with carboplatin AUC 6 IV,
paclitaxel 175mg/m2 day 1, and afatinib as a continuous daily dosing. Each cycle is repeated
every 21 days. All patients will receive concurrent chemoradiotherapy beginning 2-3 weeks
after the completion of the second cycle of induction chemotherapy (Refer to Study Schema in
page 8 of the protocol).
During the period of induction chemotherapy, a complete history and physical (including
weight) and tumor assessment by physical examination on Day 1 of each cycle will be
performed and documented. Complete blood count with differential and a comprehensive
metabolic profile will be performed weekly. After completion of induction chemotherapy,
reassessment with blood work, physical exam, CT/MRI of neck and nasopharyngolaryngoscopy
will be performed. After the completion of CRT, the patient will have a MRI, CT, or FDG PET
approximately 12 weeks after CRT. Follow-up will be standard of care from this point
Physical exam, blood work and AE assessments will also be frequently performed during entire
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
Phase I Objective: To determine the MTD or recommended Phase II dose of oral afatinib in a combination with carboplatin AUC 6 and paclitaxel 175mg/m2 q 21 days as an induction regimen in patients with AJCC stage III and IVA-B HPV(-) HNSCC of oral cavity, oropharynx, hypopharynx and larynx.
1 Year (Average)
Shanthi Marur, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Vanderbilt Ingram Cancer Center||Nashville, Tennessee 37232|
|Johns Hopkins Sidney Kimmel Comprehensive Cancer Center||Baltimore, Maryland 21231|