Back to results

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

Primary Purpose

Head and Neck Neoplasms

Status

Terminated

Phase

Phase 1

Locations

Taiwan

Study Type

Interventional

Intervention

NC-6004

Cetuximab

5-FU

About this trial

This is an interventional treatment trial for Head and Neck Neoplasms

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

National Taiwan University Hospital
Taipei Veterans General Hospital
Chang Gung Memorial Hospital, Linkou Branch

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NC-6004, Cetuximab and 5-FU

Arm Description

Cetuximab will be administered before the start of chemotherapy at a loading dose of 400 mg/m2 given, followed by a subsequent weekly doses of 250 mg/m2; NC-6004 will be administered on Day 1 every 3 weeks, and 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Incidence of AE lead to treatment discontinuation

Peak Plasma Concentration (Cmax)

Time of Maximum concentration observed (Tmax)

Area under the plasma concentration-time curve from time zero to time (AUC0-t)

Area under the concentration time-curves from time zero to infinity (AUC0-∞)

Terminal Elimination Rate Constant (λz)

Elimination Half-life (t½)

Clearance (CL) of total platinum in plasma

Clearance (CL) of total platinum in plasma ultrafiltrate

Volume of Distribution (Vz) of total platinum in plasma

Volume of Distribution (Vz) of total platinum in plasma ultrafiltrate

Tumor response rate (RR)

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 on MRI or CT results

Disease control rate (DCR)

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 on MRI or CT results

Overall response rate (ORR)

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 on MRI or CT results

Full Information

NCT ID

NCT02817113

First Posted

June 6, 2016

Last Updated

April 29, 2021

Sponsor

Orient Europharma Co., Ltd.

Collaborators

NanoCarrier Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02817113

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Terminated

Why Stopped

Strategy change

Study Start Date

June 2016 (undefined)

Primary Completion Date

September 2018 (Actual)

Study Completion Date

September 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Orient Europharma Co., Ltd.

Collaborators

NanoCarrier Co., Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed Description

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 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NC-6004, Cetuximab and 5-FU

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

NC-6004

Other Intervention Name(s)

Micelplatin (Taiwan only), Nanoplatin (Japan only)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cetuximab

Other Intervention Name(s)

Erbitux

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

5-FU

Other Intervention Name(s)

Fluorouracil

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD)

Description

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 Outcome Measure Information:

Title

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

Description

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

Time Frame

29 months

Title

Incidence of AE lead to treatment discontinuation

Time Frame

29 months

Title

Peak Plasma Concentration (Cmax)

Time Frame