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Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging (INDIRA-MISO)

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ClinicalTrials.gov Identifier: NCT03865277
Recruitment Status : Not yet recruiting
First Posted : March 6, 2019
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Mechthild Krause, Technische Universität Dresden

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Radiation: standard radiochemotherapy or dose-escalated radiochemotherapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 345 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging: Multi-center, Randomized Phase-II-trial
Estimated Study Start Date : April 7, 2019
Estimated Primary Completion Date : September 30, 2024
Estimated Study Completion Date : September 30, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
standard radiochemotherapy, hypoxic
HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to standard radiation dose, 70 Gy standard radiochemotherapy
Radiation: standard radiochemotherapy or dose-escalated radiochemotherapy

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.


Experimental: dose-escalated radiochemotherapy
HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to escalated radiation dose, 77 Gy radiochemotherapy
Radiation: standard radiochemotherapy or dose-escalated radiochemotherapy

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.


Experimental: escalated radiochemoth., carbon boost
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)
Radiation: standard radiochemotherapy or dose-escalated radiochemotherapy

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.


standard radiochemotherapy, oxic
HPV (-), oxic in 18F-MISO PET after 2 weeks of radiochemotherapy, 70 Gy standard radiochemotherapy
Radiation: standard radiochemotherapy or dose-escalated radiochemotherapy

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.


standard radiochemotherapy (70 Gy)
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.
Radiation: standard radiochemotherapy or dose-escalated radiochemotherapy

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.





Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. late toxicity [ Time Frame: 30 days to 2 years after radiochemotherapy ]
    late toxicity based on CTCAE 5.0

  2. survival [ Time Frame: 2 years after radiochemotherapy ]
    Overall survival

  3. quality of life [ Time Frame: regularly up to 2 years after radiochemotherapy ]
    EORTC-QoL Sheets specific for HNSCC and General for tumour diseases

  4. acute toxicity [ Time Frame: during treatment and up to 30 days after radiochemotherapy ]
    acute toxicity based on CTCAE 5.0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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)

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03865277


Contacts
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Contact: Mechthild Krause, Prof. Dr. +49 351 458 2238 mechthild.krause@uniklinikum-dresden.de
Contact: Esther Troost, Prof.Dr.Dr. +49 351 458 7433 esther.troost@uniklinikum-dresden.de

Locations
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Austria
Medical University of Vienna, Department of Radiation Oncology, Vienna General Hospital (AKH)
Vienna, Austria, 1090
Germany
Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology Not yet recruiting
Freiburg, Baden-Wuerttemberg, Germany, 79106
Contact: Grosu Anca, Prof. Dr.         
Department of Radiation Oncology Heidelberg University Medical School Not yet recruiting
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Contact: Jürgen Debus, Prof. Dr.         
Principal Investigator: Jürgen Debus         
Department of Radiation Oncology Not yet recruiting
Tübingen, Baden-Wuerttemberg, Germany, 72016
Contact: Daniel Zips, Prof. Dr.    +49 7071/29-8 21 65    ROInfo@med.uni-tuebingen.de   
Principal Investigator: Daniel Zips         
Mechthild Krause Not yet recruiting
Dresden, Saxony, Germany, 01307
Contact: Mechthild Krause, Prof. Dr.    +493512238    str.studien@uniklinikum-dresden.de   
Italy
Facoltà di Medicina e Chirurgia - Università Cattolica S.C. Istituto di Radiologia, Radioterapia 1
Roma, Italy, 00168
Poland
Karol-Marcinkowski Medical University of Poznan, Department of Radiation Oncology, Greater Poland Cancer Center, Department of Radiotherapy
Poznań, Poland, 61-866
Sponsors and Collaborators
Technische Universität Dresden
Investigators
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Study Chair: Mechthild Krause, Prof. University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)

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Responsible Party: Mechthild Krause, Director of the Department of Radiotherapy and Radiation Oncology, Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT03865277     History of Changes
Other Study ID Numbers: STR-INDIRA-MISO-2014
First Posted: March 6, 2019    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mechthild Krause, Technische Universität Dresden:
Head and neck cancer
radiochemotherapy
HPV

Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Hypoxia
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Signs and Symptoms, Respiratory
Signs and Symptoms
Head and Neck Neoplasms
Neoplasms by Site