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

Phase 1TerminatedNCT02817113

Orient Europharma Co., Ltd.4 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Head and Neck Neoplasms

Interventions

NC-6004DRUG

One cycle of treatment lasts for 3 weeks. NC-6004 will be administered over 1 hour on Day 1 (after the cetuximab infusion) every 3 weeks

CetuximabDRUG

One cycle of treatment lasts for 3 weeks. For each cycle, cetuximab will be administered at least 1 hour before the start of chemotherapy at a loading dose of 400 mg/m2 given over 2 hours initially (ie, on the first day of treatment), followed by a subsequent weekly doses of 250 mg/m2 over 1 hour.

5-FUDRUG

One cycle of treatment lasts for 3 weeks. 5-FU will be administered at a dose of 1,000 mg/m2/day on Day 1- Day 4 as continuous infusion every 3 weeks.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (3)

National Taiwan University Hospital

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

Chang Gung Memorial Hospital, Linkou Branch

Taoyuan District, Taiwan

Outcomes

Primary Outcomes

Maximum Tolerated Dose (MTD)

MTD of NC-6004 according to the DLT when administered in combination with 5-FU plus cetuximab as first-line treatment

Time frame: 29 months

Secondary Outcomes

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 criteria

Time frame: 29 months

Incidence of AE lead to treatment discontinuation

Time frame: 29 months

Peak Plasma Concentration (Cmax)