Ficlatuzumab and Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

Official title: A Phase 1b Study of Ficlatuzumab and Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma With Biomarker Correlatives

Status Completed

Clinical Trial Summary

The epidermal growth factor receptor (EGFR) is both oncogene and prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). EGFR's functional importance in HNSCC resulted in development of the first molecularly targeted strategy, the anti-EGFR monoclonal antibody cetuximab. Given the lack of therapeutic options for patients with recurrent/metastatic HNSCC after failure of cetuximab, there is strong scientific interest in understanding resistance in order to identify new therapies for this population. A possible resistance mechanism to anti-EGFR therapy in HNSCC is primary or compensatory activation of alternate growth factor receptors including c-Met. The MET oncogene encodes c-Met, an RTK bound exclusively by the ligand, hepatocyte growth factor (HGF). The HGF/c-Met signaling pathway converges with the EGFR network at both the PI3K/Akt and MAPK nodes. Laboratory data suggest the ability for reciprocal compensation between EGFR and c-Met. We hypothesize that HGF/c-Met pathway inhibition may overcome resistance to cetuximab in patients with HNSCC, such as those with clinical cetuximab resistance.

Ficlatuzumab (AV-299) is a humanized HGF-inhibitory immunoglobulin G1 (IgG1) monoclonal antibody. The primary objective of this phase 1b study is to find the recommended phase II dose (RP2D) of the combination of ficlatuzumab and cetuximab in patients with recurrent/metastaticHNSCC. The dose-finding study design will follow a Narayana k-in-a-row design with k set to 2 to target a 33% rate of dose-limiting toxicity (DLT). In the dose-finding phase, a total of 8 patients will be treated if no DLTs are observed or 14 patients if at least one DLT occurs. An expansion cohort will then proceed at RP2D until 12 patients have been treated at that dose level with the combination of ficlatuzumab and cetuximab. We will evaluate biomarkers of HGF/cMet pathway activation in baseline tissue, plasma and immune cells for a preliminary relationship with clinical activity.

Clinical Trial Description

This is a phase 1b, single arm, open-labeled study of ficlatuzumab and cetuximab in recurrent/metastatic HNSCC with biomarker correlatives. The primary objective of this study is to establish the recommended-for-phase II dose (RP2D) of the combination of ficlatuzumab and Cetuximab. In the absence of treatment delays due to adverse event(s), treatment may continue until disease progression or until one of the following criteria applies:

• Disease progression,

• Intercurrent illness that prevents further administration of treatment,

• Unacceptable adverse event(s),

• Patient decides to withdraw from the study, or

• General or specific changes in the patients condition render the patient unacceptable for further treatment in the judgment of the investigator.

After progressive disease, subjects will be followed for survival every 3 months for 2 years.

Cetuximab and ficlatuzumab are administered every other week on day 1 and 15 of a 28-day cycle. Ficlatuzumab will be administered as an IV infusion, over 30-60 minutes,10 mg/kg every 2 weeks, on the same day as the first dose of cetuximab. Ficlatuzumab will be administered 30-60 minutes after the completion of the cetuximab infusion. Cetuximab will be administered prior to ficlatuzumab as an IV infusion. The first dose will be administered over 120 minutes (± 15 minutes). Subsequent doses may be infused over 60 minutes (± 15 minutes).The starting dose of cetuximab (dose tier 1) will be 500 mg/m2 every 2 weeks.

Subjects will be monitored for adverse events and toxicity during study treatment and for 30 days after last dose of ficlatuzumab. Blood will be drawn for correlative studies at baseline, and at the end of every even cycle. Prior to initiation of protocol treatment, patients will undergo a mandatory research biopsy. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Carcinoma, Squamous Cell of Head and Neck
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Squamous Cell Carcinoma, Head And Neck

• NCT number: NCT02277197
• Study type: Interventional
• Source: University of Pittsburgh
• Status: Completed
• Phase: Phase 1
• Start date: August 2015
• Completion date: February 2018