on-blinded phase II study to compare the efficacy and safety of CetuGEX™ plus chemotherapy with cetuximab plus chemotherapy for the treatment of patients with stage III/IV recurrent and/or metastatic squamous cell carcinoma of the head and neck
- Conditions
- stage III/IV recurrent and/or metastatic squamous cell carcinoma of the head and neckMedDRA version: 20.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003695-13-DE
- Lead Sponsor
- Glycotope GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
1. Patients with histologically confirmed recurrent and/or metastatic SCCHN not eligible for local treatment.
2. Patients with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
3. Patients aged at least 18 years at screening.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Minimum life expectancy of 3 months.
6. Tissue samples available for specific disease and therapy related biological assessments.
7. If female and of childbearing potential, is non-lactating and has negative pregnancy test results at screening and prior to randomization.
8. If female, is 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, particulary 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 (EMA). Male patients who have partners of childbearing potential have to confirm adequate use of highly effective contraceptives during study participation until 6 months after last administration of any study medication, particulary cisplatin or carboplatin as well.
9. Willing and able to comply with the protocol.
10. Willing and able to provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
1. 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.
2. Cetuximab or other 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.
3. Surgery (other than minor interventions like diagnostic biopsy or intravenous port implantation) or irradiation within 30 days before randomization.
4. Concomitant anti-tumor therapy or concomitant immunotherapy, live vaccines including yellow fever vaccination (as per cisplatinum SmPC).
5. Concomitant corticosteroid treatment unless specified within the protocol.
6. Clinical evidence of brain metastasis or leptomeningeal involvement.
7. Patients with nasopharyngeal tumors.
8. 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 will be allowed to enter the study.
9. 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.
10. Clinically active infections = Grade 2 using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 and/or requiring intravenous antibiotics.
11. Known active hepatitis B or C.
12. Known human immunodeficiency virus (HIV) infection.
13. Myocardial infarction within 6 months prior to screening.
14. Symptomatic congestive heart failure (New York Heart Association [NYHA] 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.
15. History of keratitis requiring medical interventions within the last 5 years or interstitial lung disease.
16. Patients with any other disorder that, in the opinion of the investigator, might interfere with the conduct of the study.
17. 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.
18. Patients institutionalized by official means or court order.
19. Receipt of any other investigational medicinal product within the last 30 days before randomization or any previous CetuGEX™ administration.
20. Prior allergic reaction to a monoclonal antibody, grade 3 IRR or any grade 4 reaction to a monoclonal antibody.
21. Known sensitivity to any component of the investigational medicinal product (IMP) and medication used in this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective 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 PFS.;Secondary Objective: Secondary objectives are as follows:<br>1. To evaluate further efficacy criteria, safety and 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).<br>2. To assess PK parameters and profiles of CetuGEX™.<br>3. To assess efficacy and safety based on genetic markers for immune response (Fc?R allotypes) and biomarkers.;Primary end point(s): progression-free survival;Timepoint(s) of evaluation of this end point: Screening, every 6 weeks after day of randomization until Week 18 and every 8 weeks thereafter
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: continuously, see protocol;Secondary end point(s): Secondary efficacy endpoints include:<br>? PFS as assessed by independent centralized reading according to modified irRC.<br>? Objective response rate (ORR, i.e., CR + PR) according to modified irRC at the end of combination treatment.<br>? Best overall response rates (CR, PR, SD) according to modified irRC including maintenance therapy treatment.<br>? Clinical benefit rate (CBR, i.e., CR + PR + SD) according to modified irRC.<br>? Overall survival (OS) defined as time from randomization until death of any cause.<br>? Time to treatment failure (TTF), as defined in Section 10.3.1.2.<br>? QoL scores assessed using EORTC-QLQ-C30 and EORTC-QLQ-H&N35H.<br>In addition, PFS and all secondary efficacy endpoints listed above will be analyzed by Fc?RIIIa-allotype subgroups (i.e., FF, FV and VV), p16 status, and other potential parameters.