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

Primary Purpose

Head and Neck Squamous Cell Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
dose-escalated radiochemotherapy
dose-escalated radiochemotherapy with carbon ion boost
standard radiochemotherapy
Sponsored by
Technische Universität Dresden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring Head and neck cancer, radiochemotherapy, HPV

Eligibility Criteria

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

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

Sites / Locations

  • Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology
  • Department of Radiation Oncology Heidelberg University Medical School
  • Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie
  • Uniklinikum Wuerzburg
  • Mechthild Krause
  • Universitätsklinikum Leipzig
  • Charité University Hospital
  • Ludwig-Maximilian-Universität, Klinikum Großhadern

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Other

Experimental

Experimental

Other

Other

Arm Label

standard radiochemotherapy, hypoxic

dose-escalated radiochemotherapy, hypoxic

escalated radiochemoth., carbon boost, hypoxic

standard radiochemotherapy, oxic

standard radiochemotherapy (70 Gy)

Arm Description

HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to standard radiation dose, 70 Gy standard radiochemotherapy

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

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)

HPV (-), oxic in 18F-MISO PET after 2 weeks of radiochemotherapy, 70 Gy standard radiochemotherapy

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

late toxicity
late toxicity based on CTCAE 5.0
survival
Overall survival
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)
acute toxicity
acute toxicity based on CTCAE 5.0

Full Information

First Posted
February 26, 2019
Last Updated
September 8, 2023
Sponsor
Technische Universität Dresden
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1. Study Identification

Unique Protocol Identification Number
NCT03865277
Brief Title
Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging
Acronym
INDIRA-MISO
Official Title
Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging: Multi-center, Randomized Phase-II-trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2024 (Anticipated)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
September 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Technische Universität Dresden

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Squamous Cell Carcinoma
Keywords
Head and neck cancer, radiochemotherapy, HPV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
276 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
standard radiochemotherapy, hypoxic
Arm Type
Other
Arm Description
HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to standard radiation dose, 70 Gy standard radiochemotherapy
Arm Title
dose-escalated radiochemotherapy, hypoxic
Arm Type
Experimental
Arm Description
HPV (-), hypoxic in 18F-MISO PET after 2 weeks of radiochemotherapy, randomized to escalated radiation dose, 77 Gy radiochemotherapy
Arm Title
escalated radiochemoth., carbon boost, hypoxic
Arm Type
Experimental
Arm Description
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)
Arm Title
standard radiochemotherapy, oxic
Arm Type
Other
Arm Description
HPV (-), oxic in 18F-MISO PET after 2 weeks of radiochemotherapy, 70 Gy standard radiochemotherapy
Arm Title
standard radiochemotherapy (70 Gy)
Arm Type
Other
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
dose-escalated radiochemotherapy
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
dose-escalated radiochemotherapy with carbon ion boost
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
standard radiochemotherapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
local tumour control
Description
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).
Time Frame
Local tumor control 2 years after end of treatment
Secondary Outcome Measure Information:
Title
late toxicity
Description
late toxicity based on CTCAE 5.0
Time Frame
30 days to 2 years after radiochemotherapy
Title
survival
Description
Overall survival
Time Frame
2 years after radiochemotherapy
Title
quality of life EORTC QLQ-C30/HN-35
Description
EORTC-QLQ (C30 and HN-35) Sheets (General for tumour diseases and specific for head and neck cancer)
Time Frame
regularly up to 2 years after radiochemotherapy
Title
acute toxicity
Description
acute toxicity based on CTCAE 5.0
Time Frame
during treatment and up to 30 days after radiochemotherapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mechthild Krause, Prof. Dr.
Phone
+49 351 458 2238
Email
mechthild.krause@uniklinikum-dresden.de
First Name & Middle Initial & Last Name or Official Title & Degree
Esther Troost, Prof.Dr.Dr.
Phone
+49 351 458 7433
Email
esther.troost@uniklinikum-dresden.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mechthild Krause, Prof.
Organizational Affiliation
University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
Official's Role
Study Chair
Facility Information:
Facility Name
Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grosu Anca, Prof. Dr.
Facility Name
Department of Radiation Oncology Heidelberg University Medical School
City
Heidelberg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
69120
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jürgen Debus, Prof. Dr.
First Name & Middle Initial & Last Name & Degree
Jürgen Debus
Facility Name
Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie
City
Mannheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
68167
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frank Giordano, Prof.
Facility Name
Uniklinikum Wuerzburg
City
Würzburg
State/Province
Bavaria
ZIP/Postal Code
97080
Country
Germany
Facility Name
Mechthild Krause
City
Dresden
State/Province
Saxony
ZIP/Postal Code
01307
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mechthild Krause, Prof. Dr.
Phone
+493512238
Email
str.studien@uniklinikum-dresden.de
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
State/Province
Saxony
ZIP/Postal Code
04103
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nils Nicolay, Prof.
Facility Name
Charité University Hospital
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Volker Budach, Prof.
Facility Name
Ludwig-Maximilian-Universität, Klinikum Großhadern
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claus Belka, Prof.

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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