Head and Neck Squamous Cell CarcinomaPhase 2INDIRA-MISONCT03865277
Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging
A Phase 2 study testing dose-escalated radiochemotherapy, dose-escalated radiochemotherapy with carbon ion boost and standard radiochemotherapy in people with Head and Neck Squamous Cell Carcinoma, run by Technische Universität Dresden at 8 sites in Germany.
Trial summary
The trial evaluates the value of radiation dose escalation based on Hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- dose-escalated radiochemotherapy, dose-escalated radiochemotherapy with carbon ion boost and standard radiochemotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 276 participants
- Where
- 8 sitesGermany
- Study dates
- 1 Jul 2024to 30 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: older than 18 years
- WHO (ECOG) performance status 0-2
- Histological proven HNSCC
- HPV negative tumors or HPV positive tumors
- Stage III, IVA or IVB HNSCC according to UICC and AJCC guidelines
- Tumor classified as irresectable or patient inoperable or patient refused surgery
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- Tumor extension and localization suitable for radiochemotherapy with curative intent
- Simultaneous standard chemotherapy with cisplatin applicable (no contra-indications)
- Dental examination and -treatment before start of therapy
- For women with childbearing potential and men in reproductive ages adequate contraception.
- Ability of subject to understand character and individual consequences of the clinical trial
- Written informed consent (must be available before enrolment in the trial)
Who cannot join
- Refusal of the patients to take part in the trial
- Presence of distant metastases (UICC stage IVC)
- Previous radiotherapy in the head and neck region
- Second malignancy that is likely to require treatment during the trial intervention or follow-up period or that, in the opinion of the physician, has a considerable risk of recurrence or metastases within the follow-up period
- Serious disease or medical condition with life expectancy of less than one year
- Participation in competing interventional trial on cancer treatment
Show all 10Show fewer
- Patients who are not suitable for radiochemotherapy
- Pregnant or lactating women
- Patients not able to understand the character and individual consequences of the trial
- Nasopharyngeal Carcinomas
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Germany8 sites
Charité University Hospital
Berlin, 13353
Volker Budach, Prof.
Mechthild Krause
Dresden, Saxony, 01307
Mechthild Krause, Prof. Dr., +493512238, str.studien@uniklinikum-dresden.de
Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Grosu Anca, Prof. Dr.
Department of Radiation Oncology Heidelberg University Medical School
Heidelberg, Baden-Wurttemberg, 69120
Jürgen Debus, Prof. Dr.
Jürgen Debus
Universitätsklinikum Leipzig
Leipzig, Saxony, 04103
Nils Nicolay, Prof.
Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie
Mannheim, Baden-Wurttemberg, 68167
Frank Giordano, Prof.
Ludwig-Maximilian-Universität, Klinikum Großhadern
München, 81377
Claus Belka, Prof.
Uniklinikum Wuerzburg
Würzburg, Bavaria, 97080
About this study
Official title: Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging: Multi-center, Randomized Phase-II-trial
The trial evaluates the value of radiation dose escalation based on Hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy or radiochemotherapy with escalated radiation dose. An additional interventional arm includes a carbon ion boost. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy.
Read the detailed description
Previous preclinical data and a prospective validated patient cohort have shown that patients with head and neck squamous cell carcinoma, whose tumours are hypoxic after 2 weeks of primary radiochmeotherapy, have a significantly lower chance of locoregional tumour control. The multi-center trial evaluates the value of radiation dose escalation based on hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy (70 Gy) or radiochemotherapy with escalated radiation dose (77 Gy). An additional interventional arm includes a carbon ion boost to 77 Gy. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy. Secondary endpoints include acute and late toxicity (CTCAE 5.0), regional tumor control, overall survival, disease free survival, distant metastases, kinetics analysis of dynamic FMISO-PET scans, Quality of life (QoL). The hypothesis is that local tumour control 2 years after radiochemotherapy is higher in the dose escalated compared to the control arm.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- dose-escalated radiochemotherapy, dose-escalated radiochemotherapy with carbon ion boost, standard radiochemotherapy
- Keywords
- Head and neck cancer, radiochemotherapy, HPV
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dose-escalated radiochemotherapyRadiation
Patients will receive simultaneous radiochemotherapy, however the simultaneous chemotherapy is standard and not part of the evaluation in this trial. Present standard chemotherapy is cisplatinum 40 mg/m²/week (chemotherapy over the whole course of radiotherapy).
Radiotherapy is applied to doses of 54 Gy(RBE)/ 1.8 Gy(RBE) per fraction to the adjuvant region, 70 Gy(RBE)/ 2 Gy(RBE) per fraction to the tumor and involved lymphonodes and, if "hypoxic" and randomized to the intervention arm, 77 Gy(RBE)/ 2.2 Gy(RBE) per fraction to the primary tumor and lymphonode metastases > 2 cm.
Radiotherapy is always applied with 5 fractions per week.
dose-escalated radiochemotherapy with carbon ion boostRadiation
Patients will receive simultaneous radiochemotherapy, however the simultaneous chemotherapy is standard and not part of the evaluation in this trial.
Radiotherapy is applied to doses of 54 Gy(RBE)/ 1.8 Gy(RBE) per fraction to the adjuvant region, 70 Gy(RBE)/ 2 Gy(RBE) per fraction to the tumor and involved lymphonodes and, if "hypoxic" and treated in the study site Heidelberg, 77 Gy(RBE)/ 2.2 Gy(RBE) per fraction to the primary tumor and lymphonode metastases > 2 cm using a carbon ion boost.
Radiotherapy is always applied with 5 fractions per week.
standard radiochemotherapyRadiation
Patients will receive simultaneous radiochemotherapy, however the simultaneous chemotherapy is standard and not part of the evaluation in this trial. Present standard chemotherapy is cisplatinum 40 mg/m²/week (chemotherapy over the whole course of radiotherapy).
Radiotherapy is applied to doses of 54 Gy(RBE)/ 1.8 Gy(RBE) per fraction to the adjuvant region and 70 Gy(RBE)/ 2 Gy(RBE) per fraction to the tumor and involved lymphonodes.
Radiotherapy is always applied with 5 fractions per week.
| Study group | Role | What they receive |
|---|---|---|
| standard radiochemotherapy, hypoxic | Other | HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to standard radiation dose, 70 Gy standard radiochemotherapy Receives: Radiation: standard radiochemotherapy |
| dose-escalated radiochemotherapy, hypoxic | Experimental | HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to escalated radiation dose, 77 Gy radiochemotherapy Receives: Radiation: dose-escalated radiochemotherapy |
| escalated radiochemoth., carbon boost, hypoxic | Experimental | HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, non-randomised arm (only possible in the trial center Heidelberg), 77 Gy radiochemotherapy (boost with carbon) Receives: Radiation: dose-escalated radiochemotherapy with carbon ion boost |
| standard radiochemotherapy, oxic | Other | HPV (-), oxic in 18F-MISO PET after 2 weeks of radiochemotherapy, 70 Gy standard radiochemotherapy Receives: Radiation: standard radiochemotherapy |
| standard radiochemotherapy (70 Gy) | Other | HPV (+), HPV positive patients will get the same imaging and clinical examinations as HPV negative patients. This measure is necessary to further elucidate the prognostic role of hypoxia and HPV status and their correlation, the information will be important for consecutive clinical trials. 70 Gy standard radiochemotherapy. Receives: Radiation: standard radiochemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
local tumour control
Local tumour control (MRI, CT, PET or clinical evaluation) in the randomized dose-escalated arm compared to the randomized non dose escalated arm (arms 1 and 2).
Measured: Local tumor control 2 years after end of treatment
Secondary outcomes (4)
late toxicity
late toxicity based on CTCAE 5.0
Measured: 30 days to 2 years after radiochemotherapy
survival
Overall survival
Measured: 2 years after radiochemotherapy
quality of life EORTC QLQ-C30/HN-35
EORTC-QLQ (C30 and HN-35) Sheets (General for tumour diseases and specific for head and neck cancer)
Measured: regularly up to 2 years after radiochemotherapy
acute toxicity
acute toxicity based on CTCAE 5.0
Measured: during treatment and up to 30 days after radiochemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2019
- Study start1 Jul 2024 (estimated)
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Technische Universität DresdenThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Technische Universität Dresden
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mechthild Krause, Technische Universität Dresden
- Investigators
- Mechthild Krause, Prof., Study chair, University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03865277
- Sponsor's protocol ID
- STR-INDIRA-MISO-2014
- Acronym
- INDIRA-MISO
- Status last verified
- Sep 2023
- First submitted
- 26 Feb 2019
- Last updated
- 11 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging: Multi-center, Randomized Phase-II-trial
- ClinicalTrials.gov ID
- NCT03865277
- Acronym / sponsor ID
- INDIRA-MISO / STR-INDIRA-MISO-2014
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Keywords
- Head and neck cancer, radiochemotherapy, HPV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 276 participants (estimated)
- Lead sponsor
- Technische Universität DresdenUniversity, hospital or other
- Study start
- 1 Jul 2024 (estimated)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 6 Mar 2019 (actual)
- 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 trial evaluates the value of radiation dose escalation based on Hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy or radiochemotherapy with escalated radiation dose. An additional interventional arm includes a carbon ion boost. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy.
Detailed description
Previous preclinical data and a prospective validated patient cohort have shown that patients with head and neck squamous cell carcinoma, whose tumours are hypoxic after 2 weeks of primary radiochmeotherapy, have a significantly lower chance of locoregional tumour control. The multi-center trial evaluates the value of radiation dose escalation based on hypoxia detection by 18F_misonidazole Positron Emission Tomography (18F-MISO-PET) for primary radiochemotherapy of head and neck squamous cell carcinoma. Patients negative for human papillomavirus (HPV) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy (70 Gy) or radiochemotherapy with escalated radiation dose (77 Gy). An additional interventional arm includes a carbon ion boost to 77 Gy. HPV positive tumours can be included in a control arm. Primary endpoint is local tumour control 2 years after radiochemotherapy. Secondary endpoints include acute and late toxicity (CTCAE 5.0), regional tumor control, overall survival, disease free survival, distant metastases, kinetics analysis of dynamic FMISO-PET scans, Quality of life (QoL). The hypothesis is that local tumour control 2 years after radiochemotherapy is higher in the dose escalated compared to the control arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| standard radiochemotherapy, hypoxic | Other | Radiation: standard radiochemotherapyHPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to standard radiation dose, 70 Gy standard radiochemotherapy |
| dose-escalated radiochemotherapy, hypoxic | Experimental | Radiation: dose-escalated radiochemotherapyHPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to escalated radiation dose, 77 Gy radiochemotherapy |
| escalated radiochemoth., carbon boost, hypoxic | Experimental | Radiation: dose-escalated radiochemotherapy with carbon ion boostHPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, non-randomised arm (only possible in the trial center Heidelberg), 77 Gy radiochemotherapy (boost with carbon) |
| standard radiochemotherapy, oxic | Other | Radiation: standard radiochemotherapyHPV (-), oxic in 18F-MISO PET after 2 weeks of radiochemotherapy, 70 Gy standard radiochemotherapy |
| standard radiochemotherapy (70 Gy) | Other | Radiation: standard radiochemotherapyHPV (+), HPV positive patients will get the same imaging and clinical examinations as HPV negative patients. This measure is necessary to further elucidate the prognostic role of hypoxia and HPV status and their correlation, the information will be important for consecutive clinical trials. 70 Gy standard radiochemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age: older than 18 years
- WHO (ECOG) performance status 0-2
- Histological proven HNSCC
- HPV negative tumors or HPV positive tumors
- Stage III, IVA or IVB HNSCC according to UICC and AJCC guidelines
Key exclusion criteria (10 listed)
- Refusal of the patients to take part in the trial
- Presence of distant metastases (UICC stage IVC)
- Previous radiotherapy in the head and neck region
- Second malignancy that is likely to require treatment during the trial intervention or follow-up period or that, in the opinion of the physician, has a considerable risk of recurrence or metastases within the follow-up period
- Serious disease or medical condition with life expectancy of less than one year
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 |
|---|---|---|
| dose-escalated radiochemotherapyPatients will receive simultaneous radiochemotherapy, however the simultaneous chemotherapy is standard and not part of the evaluation in this trial. Present standard chemotherapy is cisplatinum 40 mg/m²/week (chemotherapy over the whole course of radiotherapy). Radiotherapy is applied to doses of 54 Gy(RBE)/ 1.8 Gy(RBE) per fraction to the adjuvant region, 70 Gy(RBE)/ 2 Gy(RBE) per fraction to the tumor and involved lymphonodes and, if "hypoxic" and randomized to the intervention arm, 77 Gy(RBE)/ 2.2 Gy(RBE) per fraction to the primary tumor and lymphonode metastases > 2 cm. Radiotherapy is always applied with 5 fractions per week. | Radiation | dose-escalated radiochemotherapy, hypoxic |
| dose-escalated radiochemotherapy with carbon ion boostPatients will receive simultaneous radiochemotherapy, however the simultaneous chemotherapy is standard and not part of the evaluation in this trial. Radiotherapy is applied to doses of 54 Gy(RBE)/ 1.8 Gy(RBE) per fraction to the adjuvant region, 70 Gy(RBE)/ 2 Gy(RBE) per fraction to the tumor and involved lymphonodes and, if "hypoxic" and treated in the study site Heidelberg, 77 Gy(RBE)/ 2.2 Gy(RBE) per fraction to the primary tumor and lymphonode metastases > 2 cm using a carbon ion boost. Radiotherapy is always applied with 5 fractions per week. | Radiation | escalated radiochemoth., carbon boost, hypoxic |
| standard radiochemotherapyPatients will receive simultaneous radiochemotherapy, however the simultaneous chemotherapy is standard and not part of the evaluation in this trial. Present standard chemotherapy is cisplatinum 40 mg/m²/week (chemotherapy over the whole course of radiotherapy). Radiotherapy is applied to doses of 54 Gy(RBE)/ 1.8 Gy(RBE) per fraction to the adjuvant region and 70 Gy(RBE)/ 2 Gy(RBE) per fraction to the tumor and involved lymphonodes. Radiotherapy is always applied with 5 fractions per week. | Radiation | standard radiochemotherapy (70 Gy), standard radiochemotherapy, hypoxic, standard radiochemotherapy, oxic |
Primary outcome
local tumour control
Time frame: Local tumor control 2 years after end of treatment
Local tumour control (MRI, CT, PET or clinical evaluation) in the randomized dose-escalated arm compared to the randomized non dose escalated arm (arms 1 and 2).
4 secondary outcomes
late toxicity
Time frame: 30 days to 2 years after radiochemotherapy
survival
Time frame: 2 years after radiochemotherapy
quality of life EORTC QLQ-C30/HN-35
Time frame: regularly up to 2 years after radiochemotherapy
acute toxicity
Time frame: during treatment and up to 30 days after radiochemotherapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2023.
- Individual participant dataSharing planned: Undecided
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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.
Mechthild Krause, Prof. study chair
University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dose-escalated radiochemotherapy, dose-escalated radiochemotherapy with carbon ion boost and standard radiochemotherapy in people with Head and Neck Squamous Cell Carcinoma, run by Technische Universität Dresden at 8 sites 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 12 inclusion and 10 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: opening soon, as of the sponsor's last update on 11 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mechthild Krause, Prof. Dr. (+49 351 458 2238, mechthild.krause@uniklinikum-dresden.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
local tumour control (time frame: Local tumor control 2 years after end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Sep 2023.