Study of NC-6004 in Combination With 5-FU and Cetuximab in Patients With Head and Neck Cancer

Phase I Study of NC-6004 in Combination With 5-FU and Cetuximab as First-line Treatment in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

NC-6004 is a polymeric micelle containing cisplatin as an active moiety. The nanoparticle provides sustained release of the active moiety and utilizes the enhanced permeability and retention (EPR) effect to target release of platinum to tumors. This Phase I study aims to establish a recommended dose (RD) for the triplet combination of NC-6004 plus 5-FU and cetuximab as first-line treatment in patient with recurrent and/or metastatic squamous cell carcinoma of the head and neck for further clinical study development.

1. Primary objectives

   ♦ To determine the Maximum Tolerated Dose (MTD) of NC-6004 according to the Dose Limiting Toxicity (DLT) in combination with 5-FU plus cetuximab as firstline treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN), and to decide the RD for the following studies

2. Secondary objectives 1). To evaluate the safety and tolerability profile of NC-6004 in combination with 5- FU plus cetuximab 2). To assess the pharmacokinetic effects of NC-6004 3). To assess the antitumor effects of NC-6004

Inclusion Criteria:

• Signed written informed consent
• Known (histology/cytology proven) or evidenced by radiology of recurrent and/or metastatic SCCHN not suited for local therapy
• Males or females aged ≥ 20 years and < 75 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy >12 weeks as judged by investigators
• Adequate bone marrow reservation:
• Adequate liver function:
• Adequate renal function:
• Reasonably recovered from preceding major surgery as judged by the Investigator or no major surgery within 4 weeks prior to the start of Day 1 treatment

Exclusion Criteria:

• Female of child-bearing potential who is or has intention to be pregnant or breastfeeding.
• Previous radiotherapy within 3 months before study entry
• Known brain metastasis or leptomeningeal involvement
• Marked pleural effusion or ascites above Grade 2, based on NCI-CTCAE v4.03 criteria
• History of thrombocytopenia with complications (including hemorrhage or bleeding ≥ Grade 2, based on NCI-CTCAE v4.03 criteria), hemolytic condition, or coagulation disorders that would make subjects unsafe based on the judgment of the Investigator
• Patients who have unresolved toxicity from all radiation, adjuvant/neoadjuvant chemotherapy, other targeted treatment including investigational treatment (exception of alopecia and ≤ Grade 2 peripheral neuropathy) according to NCI-CTCAE v4.03 criteria
• Known hypersensitivity to the study drugs or the drugs with similar chemical structures
• History of myocardial infarction within 6 months before study entry, unstable congestive heart failure (New York Heart Association, NYHA Stage III-IV), angina pectoris, or transient ischemic attack or cardiac arrhythmia requiring medical therapy
• History of any other cancer other than head and neck cancer (HNC) (except carcinoma in situ of the cervix) within the last 5 years.
• Primary tumor of the nasopharynx (nasopharyngeal carcinoma)
• Known HIV-1 or any active infection requiring IV antibiotics