Do Selective Radiation Dose Escalation and Tumour Hypoxia Status Impact the Locoregional Tumour Control After Radiochemotherapy of Head & Neck Tumours? (Escalox)
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Purpose
The major clinical problem and predominant cause of death after radio-oncological treatment of H+N cancers are loco-regional relapses. This randomized trial tests the hypothesis that dose escalated Intensity Modulated Radiotherapy (IMRT) selectively applied to the macroscopic primary tumor and involved neck nodes - which both in 80% - are hypoxic improves loco-regional control by at least 15% at 2 years. IMRT is combined with concurrent Cis-Platin chemotherapy. Tumor volume which correlates with number of malignant cells as well as tumor hypoxia are important biological parameters which increase radio-resistance, failure of local control and tumor progression. Basing on data of experimental and clinical radiation oncology we consider hypoxia as a useful parameter for pre-therapeutic strati-fication in future randomized radio-chemotherapy trials.
In addition, hypoxia imaging by PET can be used for testing the significance of selective dose escalation on hypoxic tumor sub-volumes ("Dose Painting").
As a prerequisite for such innovative studies addressing hypoxia the translational part investigates the following key issues: correlation between the size of total tumor volume (primary, lymph nodes) and hypoxic sub-volume, the spatial shift of the hypoxic sub-volume before start of treatment and the correlation of loco-regional control and hypoxia.
| Condition | Intervention | Phase |
|---|---|---|
|
Locally Advanced Head and Neck Cancer |
Radiation: Radiotherapy with linear accelerators |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Phase III A Prospective, Randomized, Rater-blinded, Multicentre Interventional Clinical Trial. Do Selective Radiation Dose Escalation and Tumour Hypoxia Status Impact the Locoregional Tumour Control After Radiochemotherapy of Head & Neck Tumours? |
- 2 year-loco-regional control [ Time Frame: 2 years ]
- Overall Survival (OS) [ Time Frame: 2 years ]
- Progression-free survival (PFS) [ Time Frame: 2 years ]
- Time to progression (TTP) [ Time Frame: 2 years ]
- Distant metastases (DM) [ Time Frame: 2 years ]
- Acute and late toxicity esp. concerning salivary glands [ Time Frame: 2 years ]
- Quality of life (EORTC QoL-C30, H&N 35) [ Time Frame: 2 years ]
- Adverse effects according to NCI CTC-AE (VERSION 4.0/ 10/1/2010) and LENT-SOMA [ Time Frame: 2 years ]
- FMISO PET/CT: Reproducibility and correlation with treatment coutcome [ Time Frame: 2 years ]
| Estimated Enrollment: | 250 |
| Study Start Date: | June 2013 |
| Estimated Study Completion Date: | December 2017 |
| Estimated Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: A - experimental
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.
|
Radiation: Radiotherapy with linear accelerators
Other Name: IMRT-SIB
|
|
Active Comparator: B - control
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.
|
Radiation: Radiotherapy with linear accelerators
Other Name: IMRT-SIB
|
Detailed Description:
The 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).
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
- Curative treatment intended
- 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
Contacts and Locations| Contact: Elisabeth Lindner-Pöppl | +49 (0)89-4140 ext 6328 | Eli.lindner@lrz.tum.de |
| Germany | |
| Klinik für Strahlentherapie und Radiologische Onkologie | Not yet recruiting |
| Munich, Bavaria, Germany, 81675 | |
| Contact: Steffi U. Pigorsch, Dr. med. +49 (0)89-4140 ext -5611 steffi.pigorsch@lrz.tum.de | |
| Contact: Elisabeth Lindner-Pöppl +49 (0)89-4140 ext -6328 Eli.lindner@lrz.tum.de | |
| Sub-Investigator: Steffi U. Pigorsch, Dr. med. | |
| Principal Investigator: Michael Molls, Prof. Dr. | |
| Principal Investigator: | Michael Molls, Prof. Dr. | Klinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar der TU München Ismaningerstr. 22; 81675 Munich, Germany |
More Information
No publications provided
| Responsible Party: | M. Schwaiger/Prof. Dr, Klinikum rechts der Isar (RdI) der TU München Ismaningerstr. 22; 81675 Munich, Germany |
| ClinicalTrials.gov Identifier: | NCT01212354 History of Changes |
| Other Study ID Numbers: | ESC-928-MOL-0000-I |
| Study First Received: | September 29, 2010 |
| Last Updated: | March 18, 2013 |
| Health Authority: | Germany: Bundesinstitut für Arzneimittel und Medizinprodukte Germany: Bundesamt für Strahlenschutz |
Keywords provided by Technische Universität München:
|
intensity modulated radiotherapy selective dose escalation hypoxia head cancer neck cancer |
Additional relevant MeSH terms:
|
Head and Neck Neoplasms Anoxia Neoplasms by Site |
Neoplasms Signs and Symptoms, Respiratory Signs and Symptoms |
ClinicalTrials.gov processed this record on May 19, 2013