CetuGEX™ in Comparison to Cetuximab for the Treatment of Patients With Head and Neck Cancer

Study Overview
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Brief Summary
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The aim of the study is to evaluate the efficacy of CetuGEX™ for the treatment of patients with stage III/IV recurrent and/or metastatic SCCHN as compared to cetuximab (both in combination with platinum-based chemotherapy) in terms of progression-free survival (PFS).

Detailed Description
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Indication: First line systemic treatment for stage III/IV recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) Primary Objective: To evaluate the efficacy of CetuGEX™ for the treatment of patients with stage III/IV recurrent and/or metastatic SCCHN as compared to cetuximab (both in combination with platinum-based chemotherapy) in terms of progression-free survival (PFS). Secondary Objectives: To evaluate further efficacy criteria, safety and quality of life (QoL) of patients with stage III/IV recurrent and/or metastatic SCCHN treated with CetuGEX™ as compared to cetuximab (both in combination with platinum-based chemotherapy). To assess pharmacokinetic (PK) parameters and profiles of CetuGEX™. To assess efficacy and safety based on genetic markers for immune response (Fc-gamma receptor [FcγR] allotypes) and biomarkers (exploratory only).

Official Title
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Randomized, Controlled, Open Label, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of CetuGEX™ Plus CT in Comparison to Cetuximab Plus CT in Patients With Stage III/IV Recurrent and/or Metastatic SCCHN

Conditions
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Carcinoma, Squamous Cell of Head and Neck

Intervention / Treatment
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* Drug: CetuGEX™
* Drug: Cetuximab
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed recurrent and/or metastatic SCCHN not eligible for local treatment. Patients with measurable disease according to RECIST 1.1. Patients aged at least 18 years at screening. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Minimum life expectancy of 3 months. Tissue samples available for specific and therapy-related biological assessments. If female and of childbearing potential, was non-lactating and had negative pregnancy test results at screening and prior to randomization. If female, was either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or willing to use highly effective contraceptives during study participation until 6 months after last administration of any study medication, particularly cisplatin or carboplatin, with a failure rate <1% according to the Note for Guidance on non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals (CPMP/ICH/286/95) of the European Medicines Agency. Male patients who had partners of childbearing potential had to confirm adequate use of highly effective contraceptives during study participation until 6 months after last administration of any study medication, particularly cisplatin or carboplatin, as well. Willing and able to comply with the protocol. Willing and able to provide written informed consent. Exclusion Criteria: Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to randomization. Cetuximab or other epidermal growth factor receptor (EGFR)-targeting agent treatment, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to randomization. Surgery (other than minor interventions like diagnostic biopsy or intravenous port implantation) or irradiation within 30 days before randomization. Concomitant antitumor therapy or concomitant immunotherapy, live vaccines including yellow fever vaccination (as per cisplatinum Summary of Product Characteristics [SmPC]). Concomitant corticosteroid treatment unless specified within the protocol. Clinical evidence of brain metastasis or leptomeningeal involvement. Patients with nasopharyngeal tumors. Concomitant malignant disease, except for adequately treated tumors with high likelihood of being cured (e.g., basal cell cancer of the skin, cervical cancer or breast cancer in situ). Patients with previous malignancies but without evidence of disease for at least 5 years were allowed to enter the study. Patients with renal or hepatic impairment (serum creatinine and bilirubin >1.5 fold above the upper limit of normal ranges, creatinine clearance <60 mL/min, and transaminase >5-fold above the upper limit of normal ranges) and patients with hematology parameters outside the normal ranges (hemoglobin <9 g/dL, absolute neutrophil count <1500/mm3 and platelet count <105/mm3) at screening as well as patients with impaired auditory function or platinum-related neuropathy. Clinically active infections ≥Grade 2 using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 and/or requiring intravenous antibiotics. Known active hepatitis B or C. Known human immunodeficiency virus (HIV) infection. Myocardial infarction within 6 months prior to screening. Symptomatic congestive heart failure (New York Heart Association Grade 3 or 4), unstable angina pectoris within 6 months prior to screening, significant cardiac arrhythmia, history of stroke, or transient ischemic attack within 1 year prior to screening. History of keratitis requiring medical interventions within the last 5 years or interstitial lung disease. Patients with any other disorder that, in the opinion of the investigator, might have interfered with the conduct of the study. Patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol. Patients institutionalized by official means or court order. Receipt of any other IMP within the last 30 days before randomization or any previous CetuGEX™ administration. Prior allergic reaction to a monoclonal antibody, grade 3 infusion related reaction (IRR) or any grade 4 reaction to a monoclonal antibody. Known sensitivity to any component of the IMP and medication used in this study. Known dihydropyrimidine dehydrogenase deficiency (France only).

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CetuGEX™ plus chemotherapy<br>720 mg weekly administration | Drug: CetuGEX™<br>* 60 mg/day 0, 930 mg/day 1, followed by 720 mg i.v. weekly administration<br>* Other names: Tomuzotuximab;Drug: Chemotherapy<br>* Combination of Cisplatin and 5-Fluorouracil (Carboplatin may substitute Cisplatin following the 1st cycle of therapy in case of toxicity)<br>* Other names: Combination of Cisplatin and 5-Fluorouracil;|
| Active Comparator: Cetuximab plus chemotherapy<br>250 mg/m2 weekly administration | Drug: Cetuximab<br>* 400 mg/sqm body surface area (BSA) on day 1, followed by 250 mg/sqm BSA i.v. weekly administration<br>* Other names: Erbitux®;Drug: Chemotherapy<br>* Combination of Cisplatin and 5-Fluorouracil (Carboplatin may substitute Cisplatin following the 1st cycle of therapy in case of toxicity)<br>* Other names: Combination of Cisplatin and 5-Fluorouracil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | The primary efficacy endpoint was PFS as assessed by the investigator. Date of disease progression was defined as the date of imaging (based on computed tomography (CT) scans or magnetic resonance imaging (MRI)) showing disease progression, as assessed by the investigator according to adapted immune-related RECIST 1.1 (modified irRC). Disease progression was defined as a 20% increase in tumor burden, taking as reference the smallest tumor burden recorded since the treatment started; confirmation by a second scan was not required. The PFS time was censored at the time of the last tumor assessment if the patient was alive and without progression at the last time of observation. | The PFS was defined as time from randomization until disease progression or death of any cause, up to 24 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is the percentage of patients with a tumor size reduction of a predefined amount for a minimum time period and it is defined as the sum of complete responses (CR) and partial responses (PR). CR: Disappearance of all non-nodal target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the tumor burden (sum of the longest lesion diameter (LD) of target lesions (including the short axes of any target lymph nodes plus measurable new lesions), taking as reference the baseline sum diameters. | Time from randomization until disease progression or death, whichever occurs first, up to 24 month. | 
| Clinical Benefit Rate | The clinical benefit rate is the percentage of patients with an objective response or stable disease (SD). SD is defined as not meeting criteria of complete response and partial response, in absence of meeting criteria for disease progression. Follow-up measurements must have met the SD criteria at least once after randomization at a minimum interval of 8 weeks. | Time from randomization until disease progression or death, whichever occurs first, up to 24 month. | 
| Time to Treatment Failure | Time to treatment failure is defined as the time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death. | Time to treatment failure, defined as the interval between the date of randomization and the date of treatment discontinuation for any reason, up to 24 month. | 
| Overall Survival | The overall survival is defined as the duration of time from randomization to the time of death. | Time from randomization to the time of death, up to 24 month. | 
| Time of Global Health Status Deterioration | Quality of Life (QoL) scores as assessed by European Oncology Research Trials Committee (EORTC) QoL questionnaires (QLQ) EORTC-QLQ-C30. Scores are on a scale of 0 to 100, where 100 represents the highest possible QoL.Time to first deterioration of at least 10 points. | From randomization up to end-of study visit, up to 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tomuzotuximab, cetuximab, SCCHN