CetuGEX™ in Comparison to Cetuximab for the Treatment of Patients With Head and Neck Cancer
Condition: Carcinoma, Squamous Cell of Head and Neck
MeSH terms: Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: CetuGEX™; Cetuximab; Chemotherapy
Intervention description: 60 mg/day 0, 930 mg/day 1, followed by 720 mg i.v. weekly administration; 400 mg/sqm body surface area (BSA) on day 1, followed by 250 mg/sqm BSA i.v. weekly administration; Combination of Cisplatin and 5-Fluorouracil (Carboplatin may substitute Cisplatin following the 1st cycle of therapy in case of toxicity)
Intervention MeSH terms: Cisplatin; Fluorouracil; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 240.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: tomuzotuximab; cetuximab; SCCHN

Summary:

      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).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologically confirmed recurrent and/or metastatic SCCHN not eligible
             for local treatment.

          2. Patients with measurable disease according to 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 and therapy-related biological assessments.

          7. If female and of childbearing potential, was non-lactating and had negative pregnancy
             test results at screening and prior to randomization.

          8. 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.

          9. Willing and able to comply with the protocol.

         10. Willing and able to provide written informed consent.

        Exclusion Criteria:

          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 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.

          3. Surgery (other than minor interventions like diagnostic biopsy or intravenous port
             implantation) or irradiation within 30 days before randomization.

          4. Concomitant antitumor therapy or concomitant immunotherapy, live vaccines including
             yellow fever vaccination (as per cisplatinum Summary of Product Characteristics
             [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 were 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 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 have
             interfered 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 IMP within the last 30 days before randomization or any previous
             CetuGEX™ administration.

         20. Prior allergic reaction to a monoclonal antibody, grade 3 infusion related reaction
             (IRR) or any grade 4 reaction to a monoclonal antibody.

         21. Known sensitivity to any component of the IMP and medication used in this study.

         22. Known dihydropyrimidine dehydrogenase deficiency (France only).