Induction Chemotherapy With TPF Followed by Radioimmunotherapy With Cetuximab and Intensity Modulated Radiotherapy (IMRT) Plus Carbon Ion Boost for Locally Advanced Tumors of the Oro-, Hypopharynx and Larynx: TPF-C-HIT
Inclusion Criteria:
- Signed written informed consent,
- Age of 18 to 70 years,
- Life expectancy of at least 6 month,
- Ability of subject to understand character and individual consequences of clinical
trial,
- Histologically confirmed locally advanced (stage III or IV), non-metastatic squamous
cell carcinoma of oro-, hypopharynx and larynx (T2-4, any N, M0),
- Oral cavity or oro- , hypopharynx or laynx as the primary tumor site,
- At least one uni-measurable lesion according to the RECIST criteria, Karnofsky
Performances Status > 70%,
- Adequate bone marrow function: neutrophils > 1.5 x 109/L, platelets > 100 x 109/L,
hemoglobin > 10.0 g/dL,
- Adequate liver function: Bilirubin < 1.5 mg/dL, SGOT, SGPT < 3 x ULN, GGT < 5 x ULN,
- Adequate renal function: GFR> 70 ml/min,
- Negative serum/urine Beta-HCG test in women of childbearing potential,
- Women of childbearing potential: willingness to use effective contraceptive method,
defined as the concomitant use of either an intrauterine pessary (IUP) or
contraceptive pill and in both cases, condoms for the treatment duration and 2 months
thereafter. Women of non-childbearing potiential are those who are post-menopausal
for at least 1 year or sterilized,
- Men of procreative potential: willingness for effective prevention of procreation,
defined as a use of condoms and a use of either an intrauterine pessary (IUP) or a
contraceptive pill by his partner for the treatment duration and 2 months thereafter,
- Subject's consent to collect blood and/or tumor tissue samples for proteomics and
genomics. If a patient does not consent, no samples for proteomics and genomics will
be taken. Nonetheles, he/she may be enroled in the study
Exclusion Criteria:
- Previous systemic chemotherapy, radiotherapy or surgery for carcinoma of the head,
neck and larynx,
- Nasopharyngeal Carcinoma,
- Prior exposure to EGFR pathway targeting therapy,
- Evidence of distant metastases.
- Other serious illness or medical conditions:
- Unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and
4,
- Significant neurologic or psychiatric disorders including dementia or seizures,
- Active disseminated intravascular coagulation,
- Other serious underlying medical conditions which in the opinion of investigator
could impair the ability of the patient to participate in the study,
- Symptomatic peripheral neuropathy Common Toxicity Criteria (CTC) grade 2 or higher,
- ototoxicity CTC grade 2 or higher, except if due to trauma or mechanical impairment
due to tumor mass,
- Participation in other interventional trial within the last 30 days§§,
- Surgery within the last 30 days,
- Known allergic/hypersensitivity reaction to any drugs scheduled for the study
treatment,
- Women: pregnant or breast-feeding,
- Known drug abuse,
- Other previous malignancy within 5 years, with exception of a history of a previous,
adequately treated, basal cell carcinoma of the skin or pre-invasive carcinoma of the
cervix,
- Legal incapacity or limited legal capacity,
- Medical or psychological condition which in the opinion of the investigator would not
permit the patient to complete the study or sign meaningful informed consent.