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

NCT02817113 | Terminated Phase 1 DMC

• 1 other identifier: NC-6004-006
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

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.

Conditions

Head and Neck Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

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

  29 months

• Incidence of AE lead to treatment discontinuation

  29 months

• Peak Plasma Concentration (Cmax)

  Within 4 cycles (each cycle is 21 days)

• Time of Maximum concentration observed (Tmax)

  Within 4 cycles (each cycle is 21 days)

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

  Within 4 cycles (each cycle is 21 days)

Other Outcomes (3)

• Changes in vital signs

  29 months

• Changes in laboratory results

  29 months

• Physical examination findings

  29 months

Study Arms (1)

NC-6004, Cetuximab and 5-FU

EXPERIMENTAL

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.

Drug: NC-6004; Drug: Cetuximab; Drug: 5-FU

Interventions

NC-6004 DRUG

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

Also known as: Micelplatin (Taiwan only), Nanoplatin (Japan only)

NC-6004, Cetuximab and 5-FU

Cetuximab DRUG

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.

Also known as: Erbitux

NC-6004, Cetuximab and 5-FU

5-FU DRUG

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.

Also known as: Fluorouracil

NC-6004, Cetuximab and 5-FU

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Orient Europharma Co., Ltd.: lead
• NanoCarrier Co., Ltd.: collaborator

Study Sites (3)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Memorial Hospital, Linkou Branch

Taoyuan District, 333, Taiwan

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

demplatin pegraglumer; Cetuximab; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ruey-Long Hong, MD PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2016
• First Posted: June 29, 2016
• Study Start: June 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: April 30, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (3)