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

NCT ID: NCT03865277

Last Updated: 2023-09-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2027-09-30

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

standard radiochemotherapy, hypoxic

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

Group Type: OTHER

standard radiochemotherapy

Intervention Type: RADIATION

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.

dose-escalated radiochemotherapy, hypoxic

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

Group Type: EXPERIMENTAL

dose-escalated radiochemotherapy

Intervention Type: RADIATION

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.

escalated radiochemoth., carbon boost, hypoxic

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)

Group Type: EXPERIMENTAL

dose-escalated radiochemotherapy with carbon ion boost

Intervention Type: RADIATION

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 radiochemotherapy, oxic

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

Group Type: OTHER

standard radiochemotherapy

Intervention Type: RADIATION

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.

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.

Group Type: OTHER

standard radiochemotherapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

dose-escalated radiochemotherapy with carbon ion boost

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

standard 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 and 70 Gy(RBE)/ 2 Gy(RBE) per fraction to the tumor and involved lymphonodes.

Radiotherapy is always applied with 5 fractions per week.

Intervention Type: RADIATION

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technische Universität Dresden

OTHER

Sponsor Role: lead

Responsible Party

Mechthild Krause

Director of the Department of Radiotherapy and Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mechthild Krause, Prof.

Role: STUDY_CHAIR

University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)

Locations

Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Department of Radiation Oncology Heidelberg University Medical School

Heidelberg, Baden-Wurttemberg, Germany

Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie

Mannheim, Baden-Wurttemberg, Germany

Uniklinikum Wuerzburg

Würzburg, Bavaria, Germany

Mechthild Krause

Dresden, Saxony, Germany

Universitätsklinikum Leipzig

Leipzig, Saxony, Germany

Charité University Hospital

Berlin, , Germany

Ludwig-Maximilian-Universität, Klinikum Großhadern

München, , Germany

Countries

Germany

Central Contacts

Mechthild Krause, Prof. Dr.

Role: CONTACT

mechthild.krause@uniklinikum-dresden.de

+49 351 458 2238

Esther Troost, Prof.Dr.Dr.

Role: CONTACT

esther.troost@uniklinikum-dresden.de

+49 351 458 7433

Facility Contacts

Grosu Anca, Prof. Dr.

Role: primary

Jürgen Debus, Prof. Dr.

Role: primary

Frank Giordano, Prof.

Role: primary

Mechthild Krause, Prof. Dr.

Role: primary

str.studien@uniklinikum-dresden.de

+493512238

Nils Nicolay, Prof.

Role: primary

Volker Budach, Prof.

Role: primary

Claus Belka, Prof.

Role: primary

Other Identifiers

STR-INDIRA-MISO-2014

Identifier Type: -

Identifier Source: org_study_id