inductionchemo-radio-antibody-treatment

Conditions: Squamous Cell Carcinoma of the Head; Squamous Cell Carcinoma of the Neck

Summary: this is an open-label, randomized, phase ii-study to evaluate the efficacy of a standard-tpf induction chemotherapy (ic) and an alternative tpf induction chemotherapy followed by radio-antibody-therapy, in patients with unresectable la-scc of the hn region (oro-hypopharynx carcinoma, cancer of the oral cavity). the primary objective of the study is to assess the feasibility of an experimental 'fractionated' tpf regimen compared to a current standard tpf regimen. composite endpoint of compliance and feasibility in terms of * response (recist1.1) and * hematological acute toxicity (ctcae v.4.02) * on time application of rat following an experimental or standard tpf ic. secondary endpoints are * treatment intensity achieved * toxicity (according to ctcae v.4.02) * response rates after completion of induction chemotherapy and after completion of entire protocol treatment (recist1.1) * survival (progression-free, metastasis-free, recurrence-free, overall) 1 year after randomisation * quality of life according to eortc qol c30 \& hn35 the study will be conducted at 5-6 investigational sites in germany recruiting 90 patients in total. eligible patients will have a diagnosis of histologically confirmed ssc of the hn. patients will receive one of 2 different regimens of tpf ic followed by cetuximab together with radiotherapy (rat) or a standard radiochemotherapy(rct) regimen.


Eligibility criteria:
inclusion criteria: * histologically proven unresectable scc of the oral cavity, oropharynx and hypopharynx (stage iva \& ivb) * written and signed informed consent * karnofsky ps \> 70 % * age ≥ 18 years * curative treatment intent * adequate bone marrow, hepatic and renal functions as evidenced by the following: hematology (bone marrow): * neutrophils \> 2.0 109/l * platelets \> 100 x 109/l * hemoglobin \> 10 g/dl hepatic function: * total serum bilirubin \< 1 time the unl of the participating center * asat (sgot) and alat (sgpt) \< 2.5 x unl * alkaline phosphatase \< 5 x unl renal function : * serum creatinine (sc) \< 120 µmol/l (1.4 mg/dl); * if values are \> 120 µmol/l, the creatinine clearance should be \> 60 ml/min (actual or calculated by the cockcroft-gault method as follows : weight (kg) x (140 - age) --------------------------------- k x serum creatinine serum creatinine in mg/dl: k = 72 in man k = 85 in woman serum creatinine in µmol/l: k = 0.814 in man k = 0.96 in woman • if of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing. all patients require: * dental examination and appropriate dental preservation if needed 1 week prior to the beginning of radiotherapy, * gastric feeding tube and portal-catheter. exclusion criteria: * other neoplasia within the past 5 years with the exception of a controlled skin cancer or "in situ" cervix cancer * unknown primary (cup), nasopharynx, laryngeal or salivary gland cancer * distant metastatic disease (m1) * serious co-morbidity, e.g. arteriosclerosis with apoplexy, recent myocardial infarction, high-grade carotid stenoses, unstable cardiac disease despite treatment, congestive heart failure nyha grade 3 and 4, insulin-dependent diabetes mellitus, uncontrolled hypertension, liver cirrhosis (quick \ 2mg/ml) or kidney insufficiency (creatinine \>1.4 mg/ml, the creatinine clearance should be \> 60 ml/min) * patients with asat or alat \> 2.5 unl associated with alkaline phosphatase \> 5 unl are not eligible for the study * known hiv-infection * pregnancy or lactation * women of child-bearing potential with unclear contraception * previous treatment of the disease with chemotherapy, radiotherapy, egfr-targeting agents or surgery exceeding biopsy in head and neck * concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening * social situations that limit compliance with study requirements * deficient dental preservation status or not accomplished wound healing * legal incapacity * prior accommodation in an institution under officially or judicially orders (§ 40 1 p. 3 no. 4 amg) * symptomatic peripheral neuropathy national cancer institute-common toxicity criteria (nci-ctc) grade 2 and/or ototoxicity grade 2, except if due to trauma or mechanical impairment due to tumor mass * known allergic/hypersensitivity reaction to any of the components of the treatment

Keywords: induction chemotherapy radiotherapy locally advanced head neck tumor toxicity la scchn unresectable squamous cell cancer of the head and neck, stage iv (uicc)