InductionChemo-Radio-Antibody-Treatment

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 \< 75%, total protein \<3.0 g/dl, bilirubin \>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