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Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT (Escalox)

Primary Purpose

Locally Advanced Head and Neck Cancer

Status

Recruiting

Phase

Phase 3

Locations

Germany

Study Type

Interventional

Intervention

Radiotherapy

About this trial

This is an interventional treatment trial for Locally Advanced Head and Neck Cancer focused on measuring intensity modulated radiotherapy, selective dose escalation, hypoxia, head cancer, neck cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Klinik für RadioOnkologie StrahlentherapieRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

A - experimental

B - control

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

2 year-loco-regional control

Secondary Outcome Measures

Overall Survival (OS)

Progression-free survival (PFS)

Time to progression (TTP)

Distant metastases (DM)

Acute and late toxicity esp. concerning salivary glands

Quality of life (EORTC QoL-C30, H&N 35)

Adverse effects according to NCI CTC-AE (VERSION 4.0/ 10/1/2010) and LENT-SOMA

FMISO PET/CT: Reproducibility and correlation with treatment coutcome

Relapse free Survival (RFS)

Full Information

NCT ID

NCT01212354

First Posted

September 29, 2010

Last Updated

February 8, 2016

Sponsor

Technical University of Munich

1. Study Identification

Unique Protocol Identification Number

NCT01212354

Brief Title

Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT

Acronym

Escalox

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?

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Recruiting

Study Start Date

July 2015 (undefined)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Technical University of Munich

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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. Before starting the main study a pre-study to assess the occurrence of radiation induced toxicities is mandatory to be performed. In a step-wise dose-escalation in a cohort-design the safety of dose-escalation should be determined. Step one: 6 patients Step two: 14 patients. In the pre-study the 1st group (6 patients) should be treated with 2.2 Gy up to 77.0 Gy for DEVPT and DEVLK. After evaluation of the toxicity the next 14 patients should be treated by this scheme.

Detailed Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Locally Advanced Head and Neck Cancer

Keywords

intensity modulated radiotherapy, selective dose escalation, hypoxia, head cancer, neck cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

270 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

A - experimental

Arm Type

Experimental

Arm Description

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.

Arm Title

B - control

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Other Intervention Name(s)

IMRT-SIB

Intervention Description

7 weeks Radiation dose escalation (5 x 2.3 Gy up to 80.5 Gy total dose)

Primary Outcome Measure Information:

Title

2 year-loco-regional control

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Time Frame

2 years

Title

Progression-free survival (PFS)

Time Frame

2 years

Title

Time to progression (TTP)

Time Frame

5 years

Title

Distant metastases (DM)

Time Frame

2 years

Title

Acute and late toxicity esp. concerning salivary glands

Time Frame

5 years

Title

Quality of life (EORTC QoL-C30, H&N 35)

Time Frame

2 years

Title

Adverse effects according to NCI CTC-AE (VERSION 4.0/ 10/1/2010) and LENT-SOMA

Time Frame

2 years

Title

FMISO PET/CT: Reproducibility and correlation with treatment coutcome

Time Frame

2 years

Title

Relapse free Survival (RFS)

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sabine Barta, Dr.

Phone

+49 (0)89-4140

Ext

7787

sabine.barta@mri.tum.de

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steffi U. Pigorsch, Dr. med.

Organizational Affiliation

Klinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar der TU München Ismaningerstr. 22; 81675 Munich, Germany

Official's Role

Principal Investigator

Facility Information:

Facility Name

Klinik für RadioOnkologie Strahlentherapie

City

Munich

State/Province

Bavaria

ZIP/Postal Code

81675

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Steffi U. Pigorsch, Dr. med.

Phone

+49 (0)89-4140

Ext

-5611

steffi.pigorsch@lrz.tum.de

First Name & Middle Initial & Last Name & Degree

Sabine Barta, Dr.

Phone

+49 (0)89-4140

Ext

7787

sabine.barta@mri.tum.de

First Name & Middle Initial & Last Name & Degree

Steffi U. Pigorsch, Dr. med.

First Name & Middle Initial & Last Name & Degree

Stephanie Combs, Prof. Dr.

12. IPD Sharing Statement

Citations:

PubMed Identifier

33138837

Citation

Pigorsch SU, Kampfer S, Oechsner M, Mayinger MC, Mozes P, Devecka M, Kessel KK, Combs SE, Wilkens JJ. Report on planning comparison of VMAT, IMRT and helical tomotherapy for the ESCALOX-trial pre-study. Radiat Oncol. 2020 Nov 2;15(1):253. doi: 10.1186/s13014-020-01693-2.

Results Reference

derived

PubMed Identifier

28249612

Citation

Pigorsch SU, Wilkens JJ, Kampfer S, Kehl V, Hapfelmeier A, Schlager C, Bier H, Schwaiger M, Combs SE. Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol. Radiat Oncol. 2017 Mar 1;12(1):45. doi: 10.1186/s13014-017-0776-1.

Results Reference

derived

Learn more about this trial

Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT

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