This study tests the hypothesis that the Radiation dose escalation to the macroscopic Tumor improves the locoregional control survival after concomitant chemoradiation over 2 years. As a translational objective the pre-therapeutic [18F]-FMISO PET Imaging of Tumor hypoxia is investigated as a useful croterion for stratification, especially with regard to prediction of improved locoregional Tumor control by dose escalation for further clinical studies. MedDRA version: 18.0 Level: PT Classifica
Conditions
Interventions
Trade Name: 18F-FMISO
Product Name: [18F]-FMISO
Pharmaceutical Form: Injection
INN or Proposed INN: MISONIDAZOLE
CAS Number: 13551-87-6
Concentration unit: MBq megabecquerel(s)
Concentration type: equ
Sponsors
Technische Universität München Fakultät für Medizin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed written informed consent • Age = 18 = 70 years • Independent of gender • Independent of race • ECOG 0 – 2 • Tumor of oral cavity,oropharynx or hypopharynx • Histology: squamous cell carcinoma • Curativ etreatment intended • Tumor is classified as irresectable (see Appendix) • Woman of child-bearing age: negative pregnancy testin 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Patients are not eligible for this study if they fulfill one or more of the following 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 < 1 year • contraindications to receive Cisplatin • social situations that limit compliance with study requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Following the requirements of the Bundesamt für Strahlenschutz the primary objective of the pre-study is to assess the occurence of radiogenic toxicities. The main Escalox-trial hypothesizes an improvement in the 2-year loco-regional tumor control and survival in patients of explorative trial arm A in comparison to patients of arm B which undergo standard radiotherapy due to the use of Radiation dose escalation to a sub-volume of the gross tumor volume of locally advanced head and neck cancer in arm A. Primary objective: Does a selective radiation dose escalation to gross Tumor volume improve loco-regional control and survival over 2 years? ;Secondary Objective: The secondary objective of the main study is to assess survival, disease progression, toxicity and quality of life. In an subset of patients it is planned to assess the Signal stability of static pretherapeutic Imaging with 18F-FMISO PET Imaging, to assess by use of the additional acquisition of dynamic PET data ist accuracy regarding the identification of hypoxic Tumor sub-regions and patinet outcome, and to assess as a translational objective the pre-therapeutic 18-F-FMISO PET Imaging of Tumor hypoxia is investigated as a useful criterion for stratification, especially with regard to prediction of improved loco-regional Tumor control by dose escalation for further clinical studies;Primary end point(s): The primary toxicity endpoint of the pre-study the occurrence of radiaton induced toxicities reported regarding CTCAE 4.0. The primary efficacy endpoint of the main trial is the loco-regional control (LRC)-survival over two years. It is defined as the time to local relapse or death. ;Timepoint(s) of evaluation of this end point: 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall Survival (OS) over 2 years • Progression-free Survival (PFS) over 2 years • Relapse-free Survival (RFS) over 2 years • Time to Progression (TTP) over 5 years • Occurrence of Distant Metastases (DM) • Acute and late toxicity esp. concerning salivary glands • Quality of life (EORTC, H&N 35) • Adverse effects according to NCI CTC-AE (VERSION 4.0/ 01/10/ 2010) and LENT-SOMA In a subset of patients, the following secondary endpoints will be assessed: • Mean amount of temporal shift of hypoxic areas (% overlap) • Static 18-F-FMISO PET parameters: hypoxic volume (HV), hypoxic fraction (HF), visual assessment (semiquantitative scoring), maximum tumour to blood activity ratio (T:Bmax), maximum tumour to muscle activity ratio (T:Mmax); each for single lesions (primary and cervical metastases) and total tumour mass. • Temporal shift of hypoxic volumes: total hypoxic volume (THV), overlapping hypoxic volume (OHV), non-overlapping hypoxic volume (N-OHV), ?HV (HV1-HV2), ?HF (HF1-HF2), ?T:Bmax (T:Bmax(1)-T:Bmax(2)), ?T:Mmax (T:Mmax(1)-T:Mmax(2)), ?score (score1-score2); each for single lesions (primary and cervical metastases) and total tumour mass. • Correlation of in-field relapses with hypoxic areas: 1. oxygenated area, 2. non-overlapping hypoxic area, 3. overlapping hypoxic area. • Value of additional acquisition of dynamic PET data to improve the accuracy of static PET (e.g. Thorwarth model). | — |
Countries
Germany
Contacts
Public ContactDr. Sabine Barta
Münchner Studienzentrum
Outcome results
None listed