Squamous Cell Carcinoma of the Head, Squamous Cell Carcinoma of the Neck
Conditions
Keywords
induction chemotherapy, radiotherapy, locally advanced head neck tumor, toxicity, LA SCCHN, Unresectable squamous cell cancer of the head and neck,, Stage IV (UICC)
Brief 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.
Interventions
Docetaxel 75 mg/m2 d 1 Cis-platinum 75 mg/m2 d 1 5-FU 750 mg/m2/d c.i. d 1-4 Cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX
DRUGTPF experimental
Docetaxel 40 mg/m2 d 1+8 Cis-platinum 40 mg/m2 d 1+8 5-FU 1500 mg/m2/24h c.i. d 1+8 every 21 day for 3 cycles 2. Antibody therapy with: cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX
RADIATIONStandard Radiochemotherapy (HART)
Hyperfractionated accelerated radiotherapy with concurrent Cisplatin and 5-Fluorouracil chemotherapy
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen. | August 2010- December 2012 | acute hematological toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival and late morbidity | 1 year | All adequate items illustrating acute toxicity and late morbidity, in particular by hematological measures until one year after treatment (according to NCI-CTCAE v.4.02) Survival (progression-free, metastases-free, recurrence-free, Overall survival) after 1 year Response rates after TPF IC (RECIST1.1) Response rates after completion of multimodal treatment (see follow-up for scheduling RECIST1.1) Efficacy in relation to HPV status (p16 IHC) Quality of life according to EORTC QLC-30 & HN35 |
Countries
Germany
Outcome results
None listed