NC-6004 With 5-FU and Cetuximab for Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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Part 1 of this study will establish a recommended Phase II (RPII) dose for the triplet combination of NC-6004 plus 5-Fluorouracil (5-FU) and cetuximab. Part 2 will provide the efficacy signal of the triplet combination in this patient population.

Detailed Description
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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.

Official Title
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Phase I/II Clinical Trial of NC-6004 in Combination With 5-FU and Cetuximab as First-line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Carcinoma, Squamous Cell of Head and Neck

Intervention / Treatment
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* Drug: NC-6004
* Drug: Cetuximab
* Drug: 5-FU


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NC-6004 and 5-FU<br>Phase I, continual reassessment method, dose-escalation study to determine the maximum tolerated dose (MTD) and an RPII dose of NC-6004 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. In Part 1, patients will be assigned to receive cetuximab followed by NC-6004 and 5-FU. Phase II, adaptive, open-label expansion study evaluating the activity, safety, and tolerability of NC-6004 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck at the RPII dose identified in Part 1. In Part 2, all patients will receive NC-6004 at the RPII dose established in Part 1, in combination with cetuximab and 5-FU according to the same schedule as used in Part 1. | Drug: NC-6004<br>* NC-6004 provided by NanoCarrier<br>Drug: Cetuximab<br>* Commercially Available<br>Drug: 5-FU<br>* Commercially Available<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RPII dose for the combination of NC-6004 plus 5-FU plus cetuximab. | Part 1: To determine dose limiting toxicities and the RPII dose | Up to day 90 | 
| Progression free survival in patients following treatment with NC-6004 plus 5-FU plus cetuximab. | 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. | Up to day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | 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). | Up to day 90 | 
| EORTC QLQ-C30 | Least squares mean estimates for health-related quality of life (HRQOL) scores over time | Up to day 90 | 
| QLQ-Head and Neck 35 | Least squares mean estimates for health-related quality of life (HRQOL) scores over time | Up to day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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squamous cell carcinoma, head, neck