Locally Advanced Head and Neck CancerPhase 3EscaloxNCT01212354
Impact of Selective Radiation Dose Escalation and Tumour Hypoxia Status on Locoregional Tumour Control After Radiochemotherapy of HNT
A Phase 3 study testing Radiotherapy in people with Locally Advanced Head and Neck Cancer, run by Technical University of Munich at 1 site in Germany.
Trial 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 … Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Locally Advanced Head and Neck Cancer
- What is being tested?
- Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2015to Sep 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent
- Age ≥ 18 ≤ 70 years
- Independent of gender
- Independent of race
- ECOG 0 - 2
- Tumor of oral cavity, oropharynx or hypopharynx
Show all 16Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Klinik für RadioOnkologie Strahlentherapie
Munich, Bavaria, 81675
Steffi U. Pigorsch, Dr. med., +49 (0)89-4140 ext. -5611, steffi.pigorsch@lrz.tum.de
Sabine Barta, Dr., +49 (0)89-4140 ext. 7787, sabine.barta@mri.tum.de
About this study
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?
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").
Read more
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.
Read the 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).
- Conditions
- Locally Advanced Head and Neck Cancer
- Being tested
- Radiotherapy
- Keywords
- intensity modulated radiotherapy, selective dose escalation, hypoxia, head cancer, neck cancer
- Medical subject headings
- Head and Neck Neoplasms, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
Also called IMRT-SIB
7 weeks Radiation dose escalation (5 x 2.3 Gy up to 80.5 Gy total dose)
| Study group | Role | What they receive |
|---|---|---|
| A - experimental | 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. Receives: Radiation: Radiotherapy |
| B - control | Active comparator | 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. Receives: Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
2 year-loco-regional control
Measured: 2 years
Secondary outcomes (9)
Overall Survival (OS)
Measured: 2 years
Progression-free survival (PFS)
Measured: 2 years
Time to progression (TTP)
Measured: 5 years
Distant metastases (DM)
Measured: 2 years
Acute and late toxicity esp. concerning salivary glands
Measured: 5 years
Quality of life (EORTC QoL-C30, H&N 35)
Measured: 2 years
Adverse effects according to NCI CTC-AE (VERSION 4.0/ 10/1/2010) and LENT-SOMA
Measured: 2 years
FMISO PET/CT: Reproducibility and correlation with treatment coutcome
Measured: 2 years
Relapse free Survival (RFS)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2010 (estimated)
- Study startJul 2015
- Primary completionJan 2025 (estimated)
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Technical University of MunichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01212354
- Sponsor's protocol ID
- ESC-928-MOL-0000-I
- Acronym
- Escalox
- Status last verified
- Feb 2016
- First submitted
- 29 Sep 2010
- Last updated
- 9 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33138837Pigorsch 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.
PubMed 28249612
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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?
- ClinicalTrials.gov ID
- NCT01212354
- Acronym / sponsor ID
- Escalox / ESC-928-MOL-0000-I
- Conditions
- Locally Advanced Head and Neck Cancer
- Keywords
- intensity modulated radiotherapy, selective dose escalation, hypoxia, head cancer, neck cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 30 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A - experimental | Experimental | Radiation: Radiotherapy7 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. |
| B - control | Active comparator | Radiation: Radiotherapy7 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Signed written informed consent
- Age ≥ 18 ≤ 70 years
- Independent of gender
- Independent of race
- ECOG 0 - 2
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RadiotherapyAlso: IMRT-SIB7 weeks Radiation dose escalation (5 x 2.3 Gy up to 80.5 Gy total dose) | Radiation | A - experimental, B - control |
Primary outcome
2 year-loco-regional control
Time frame: 2 years
9 secondary outcomes
Overall Survival (OS)
Time frame: 2 years
Progression-free survival (PFS)
Time frame: 2 years
Time to progression (TTP)
Time frame: 5 years
Distant metastases (DM)
Time frame: 2 years
Acute and late toxicity esp. concerning salivary glands
Time frame: 5 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
Relapse free Survival (RFS)
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2016.
- Derived from this study: PubMed 33138837Pigorsch 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.
- Derived from this study: PubMed 28249612Pigorsch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Radiotherapy in people with Locally Advanced Head and Neck Cancer, run by Technical University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sabine Barta, Dr. (+49 (0)89-4140 ext. 7787, sabine.barta@mri.tum.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2 year-loco-regional control (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01212354, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2016.