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

Head and Neck Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02817113
• Other study ID #: NC-6004-006
• Status: Terminated
• Phase: Phase 1
• Start date: June 2016
• Est. completion date: September 2018

Study information

• Verified date: April 2021
• Source: Orient Europharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Neoplasms

Intervention

Drug:
• NC-6004
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
• Cetuximab
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-FU
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.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou Branch	Taoyuan

Sponsors (2)

Lead Sponsor	Collaborator
Orient Europharma Co., Ltd.	NanoCarrier Co., Ltd.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in vital signs	Arterial blood pressure, heart rate, respiratory rate and temperature are to be monitored during infusion.	29 months
Other	Changes in laboratory results	Number of participants with abnormal laboratory values and/or adverse events that are related to treatment.	29 months
Other	Physical examination findings	Number of participants with physical examination abnormal findings that are related to treatment.	29 months
Primary	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	29 months
Secondary	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	29 months
Secondary	Incidence of AE lead to treatment discontinuation		29 months
Secondary	Peak Plasma Concentration (Cmax)		Within 4 cycles (each cycle is 21 days)
Secondary	Time of Maximum concentration observed (Tmax)		Within 4 cycles (each cycle is 21 days)
Secondary	Area under the plasma concentration-time curve from time zero to time (AUC0-t)		Within 4 cycles (each cycle is 21 days)
Secondary	Area under the concentration time-curves from time zero to infinity (AUC0-8)		Within 4 cycles (each cycle is 21 days)
Secondary	Terminal Elimination Rate Constant (?z)		Within 4 cycles (each cycle is 21 days)
Secondary	Elimination Half-life (t½)		Within 4 cycles (each cycle is 21 days)
Secondary	Clearance (CL) of total platinum in plasma		Within 4 cycles (each cycle is 21 days)
Secondary	Clearance (CL) of total platinum in plasma ultrafiltrate		Within 4 cycles (each cycle is 21 days)
Secondary	Volume of Distribution (Vz) of total platinum in plasma		Within 4 cycles (each cycle is 21 days)
Secondary	Volume of Distribution (Vz) of total platinum in plasma ultrafiltrate		Within 4 cycles (each cycle is 21 days)
Secondary	Tumor response rate (RR)	Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 on MRI or CT results	29 months
Secondary	Disease control rate (DCR)	Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 on MRI or CT results	29 months
Secondary	Overall response rate (ORR)	Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 on MRI or CT results	29 months