NC-6004 With 5-FU and Cetuximab for Treatment of Recurrent 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 effect to target release of platinum to tumors. Currently available nonclinical data and enhanced pharmacokinetics suggest that NC-6004 has the potential to be more active than cisplatin, with increased tolerability.

• NC-6004 (Drug): NC-6004 provided by NanoCarrier
• Cetuximab (Drug): Commercially Available
• 5-FU (Drug): Commercially Available

Primary outcomes

• RPII dose for the combination of NC-6004 plus 5-FU plus cetuximab. [Up to day 90]: Part 1: To determine dose limiting toxicities and the RPII dose
• Progression free survival in patients following treatment with NC-6004 plus 5-FU plus cetuximab. [Up to day 90]: Part 2: To determine the median PFS in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after treatment with NC-6004 plus cetuximab plus 5-FU.

Secondary outcomes

• Overall response rate [Up to day 90]: To evaluate overall response rate (ORR), duration of response (DOR), disease control rate (DCR = complete response \[CR\] + partial response \[PR\] +stable disease), duration of stable disease (DSD), and overall survival (OS).
• EORTC QLQ-C30 [Up to day 90]: Least squares mean estimates for health-related quality of life (HRQOL) scores over time
• QLQ-Head and Neck 35 [Up to day 90]: Least squares mean estimates for health-related quality of life (HRQOL) scores over time

Other outcomes

• Incidence and severity of AEs and laboratory abnormalities [Up to day 90]: Incidence and severity of AEs and laboratory abnormalities, according to the NCI CTCAE v4.03 criteria.
• Occurrence of SAEs and treatment discontinuations due to AEs [Up to day 90]: Adverse events will be summarized by dose level, in subsets of all TEAEs, and by all treatment-related AEs. Clinical laboratory and vital sign measurements will be summarized by dose level and change from baseline.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of stage III/IV recurrent and/or metastatic squamous cell carcinoma of the head and neck not suited for local therapy
* Measurable disease, as defined by RECIST v1.1
* ECOG performance status 0-1
* Adequate bone marrow reserve
* Adequate liver and renal function
* Have a negative pregnancy test result at Screening for females of childbearing potential
* Male patients must agree to use a condom during treatment and for 90 days after dosing and must agree not to donate sperm for 90 days after dosing
* Women of childbearing potential are willing to agree to use 1 of the study-defined effective methods of birth control from the time of study entry to 6 months after the last day of treatment
* 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:

* Nasopharyngeal carcinoma
* Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 3 months before Day 1 or more than 6 months prior to Day 1 if platinum-based
* Concomitant anticancer therapy, systemic immune therapy, or hormonal therapy as cancer therapy
* Unresolved toxicity from all radiation, adjuvant/ neoadjuvant chemotherapy, other targeted treatment including investigational treatment
* History of thrombocytopenia with complications
* Known hypersensitivity to platinum compounds
* Pregnant or breastfeeding
* Active infection (infection requiring intravenous antibiotics)
* Uncontrolled hypertension
* Malignancies other than head and neck cancer within 5 years prior to Day 1 of treatment, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
* Signs or symptoms of organ failure, major chronic illnesses other than cancer, or any concomitant medical or social conditions which, in the opinion of the investigator, make it undesirable for the patient to participate in the study, or which could jeopardize compliance with the protocol
* Have experienced any of the following within the 6-month period prior to Screening: unstable angina pectoris, clinically significant coronary artery disease, cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40%, or cardiac arrhythmia
* Any investigational treatment within 30 days or 5 half-lives, whichever is longer, of Day 1 of treatment
* Patient is unwilling or unable to comply with study procedures, or is planning to take vacation for 7 or more consecutive days during the treatment phase of the study without prior consent from the medical monitor
* Any other medical or social condition that, in the opinion of the investigator, would not permit the patient to complete the study or sign informed consent

• Atsushi Osada, Study Director, Study director, NanoCarrier Co., Ltd.