Do Selective Radiation Dose Escalation and Tumour Hypoxia Status Impact the Locoregional Tumour Control After Radiochemotherapy of Head & Neck Tumours? (Escalox)

This study is not yet open for participant recruitment.
Verified November 2013 by Technische Universität München
Sponsor:
Information provided by (Responsible Party):
Technische Universität München
ClinicalTrials.gov Identifier:
NCT01212354
First received: September 29, 2010
Last updated: November 27, 2013
Last verified: November 2013
  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?

Resource links provided by NLM:


Further study details as provided by Technische Universität München:

Primary Outcome Measures:
  • 2 year-loco-regional control [ Time Frame: 2 years ]

Secondary Outcome Measures:
  • 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
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
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01212354

Contacts
Contact: Elisabeth Lindner-Pöppl +49 (0)89-4140 ext 6328 Eli.lindner@lrz.tum.de

Locations
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.         
Sponsors and Collaborators
Technische Universität München
Investigators
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: Technische Universität München
ClinicalTrials.gov Identifier: NCT01212354     History of Changes
Other Study ID Numbers: ESC-928-MOL-0000-I
Study First Received: September 29, 2010
Last Updated: November 27, 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 April 15, 2014