Indikation (Clinical Trials):
Head and Neck Neoplasms, Hypoxia
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 3
Sponsor:
Technische Universität München
Collaborator:
-
Studienleiter
Steffi U. Pigorsch, Dr. med. Principal Investigator Klinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar der TU München Ismaningerstr. 22; 81675 Munich, Germany
The pre-study with sequential design is a prospective multicentre interventional pilot study
to assess toxicity of intensity modulated radiotherapy (IMRT) plus Cisplatin of head and neck
cancers
The main study is a multicenter phase III randomized trial on the effect of dose escalated
radiotherapy with concomitant chemotherapy to treat local advanced head and neck cancer. The
study compares two treatment arms:
Experimental intervention (group A): 7 weeks standard radio-chemotherapy with 20 mg/m²/d
Cisplatin in week 1 and 5 including simultaneous radiation dose escalation (5x2.3 Gy per week
up to 80.5 Gy total dose) to the primary tumour and involved neck nodes ≥ 2 cm.
The Dose Escalated tumour Volume (DEVPT) is defined by the macroscopic (Gross) primary Tumour
Volume (GTVPT) minus a 3 mm margin at organs at risk or at mucosal sites to reduce the risk
of high dose deposition at the surrounding normal tissue. All involved lymph nodes visualized
by CT with a minimal diameter of 2 cm are also included for dose escalation (DEVLN). The
DEVLN of the lymph nodes > 2 cm is determined by the involved lymph node volume (GTVLN) minus
a margin of 3 mm at organs at risk or mucosal sites. The 3 mm margin as well as the part of
the target volume with suspected microscopic tumor extension receives 2 Gy per fraction.
Control intervention (group B): 7 weeks standard radio-chemotherapy with 5x2.0 Gy per week up
to a total dose of 70 Gy and 20 mg/m²/d Cisplatin in week 1 and 5.
In group A and B: The treatment of the elective cervical lymphatic areas is given in the same
session as the GTV but with a single dose of 1.6 Gy up to 56 Gy (so called simultaneous
integrated boost concept).
- Tumor is classified as irresectable (see Appendix)
- Woman of child-bearing age: negative pregnancy test in serum
- Contraception in male and female patients and their partners if of childbearing
potential, willingness to use effective contraceptive method for the study duration
and 2 months post therapy
- Sufficient bone marrow reserves during 7 days before study inclusion; (leukocytes ≥ 4
x 109/l, absolute no. of neutrophiles (ANC) ≥ 2 x 109/; thrombocyte count ≥ 100 x
109/l; Hemoglobin ≥ 10g/dl)
- adequate liver function during 7 days before study inclusion (total bilirubine ≤ 2,5 x
ULN (upper limit of normal), ASAT/ ALAT ≤ 2,5 x ULN, alkaline phosphatase ≤ 2,5 x ULN
of the institution's normal value)
- adequate kidney function during 7 days before study inclusion; serum creatinine ≤ 130
μmol/l; creatinine clearance ≥ 70 ml/min
- all patients should have a dental examination before starting therapy and when
necessary be treated, adaptation of a teeth protection bar
- a percutane feeding tube should be applied before start of treatment
Exclusion Criteria:
- Infiltration of the mandible and / or larynx
- impaired renal and/ or liver function
- secondary malignancy, unknown primary cancer, nasopharynx cancer or salivary gland
cancers
- Metastatic disease
- Another cancer within 5 years of study entry
- Serious concomitant disease or medical condition
- Pregnancy or lactation
- Women of child-bearing potential with unclear contraception (post menopausal women
must have been amenorrheal for at least 12 months to be considered of non-childbearing
potential)
- previous treatment with chemotherapy, radiotherapy or surgery in head and neck (except
an excisional biopsy or biopsy for histology)
- concurrent treatment with other experimental drugs or participation in another
clinical trial with any investigational drug within 30 days prior to study screening
- life expectancy of < 12 months
- contraindications to receive Cisplatin
- social situations that limit compliance with study requirements
Experimental: A - experimental 7 weeks Radiotherapy Intervention with with 5x2.3 Gy per week up to a total dose of 80.5 Gy and parallel chemotherapy of 20 mg/m²/d Cisplatin in week 1 and 5.
Active Comparator: B - control 7 weeks Radiotherapy Intervention with 5x2.0 Gy per week up to a total dose of 70 Gy and parallel chemotherapy of 20 mg/m²/d Cisplatin in week 1 and 5.
