Ficlatuzumab, Cisplatin and IMRT in Locally Advanced Head and Neck Squamous Cell Carcinoma
Status:
Terminated
Trial end date:
2016-09-01
Target enrollment:
Participant gender:
Summary
Head and neck squamous cell carcinoma (HNSCC) is the most common cancer arising in the upper
aerodigestive tract, and is the sixth leading incident cancer worldwide. Despite advances in
multimodality therapy, 5-year overall survival (OS) is 40-60%, and has increased only
incrementally in the past two decades. The current standard of care for primary nonsurgical
management of locally advanced HNSCC is concurrent cisplatin-radiotheray, which significantly
improved OS, progression-free survival, and locoregional control compared with radiotherapy
alone in the landmark Intergroup trial 0126.
The MET proto-oncogene encodes c-Met, a heterodimeric growth factor receptor bound
exclusively by its ligand, hepatocyte growth factor (HGF). In the laboratory, activation of
the HGF/c-Met pathway is associated with resistance to cisplatin and radiotherapy in HNSCC.
We hypothesize that the addition of an HGF/c-Met pathway inhibitor to cisplatin-radiotherapy
may improve outcomes in HNSCC. Ficlatuzumab (AV-299) is a humanized HGF-inhibitory IgG1
monoclonal antibody.
The primary objective of this study is to establish the recommended phase II dose (RP2D) of
the combination of ficlatuzumab, cisplatin and intensity-modulated radiotherapy (IMRT), in
patients with locally advanced HNSCC. The dose-finding study design will follow a Narayana
k-in-a-row design with k set to 3 to target a 33% DLT rate. In the dose-finding phase, a
total of either 10 or 14 patients will be treated. If no DLTs are observed among 10 patients,
the highest dose tier will be declared the RP2D. Otherwise the RP2D will be estimated from
DLTs across all dose levels by isotonic regression. The secondary objective is to estimate
biomarker association with preliminary clinical response. We will evaluate biomarkers of
HGF/cMet pathway activation in tumor tissue, plasma, and immune cells.