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

NCT03865277 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: STR-INDIRA-MISO-2014
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 8

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Head and neck cancer; radiochemotherapy; HPV

Outcome Measures

Primary Outcomes (1)

• 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).

  Local tumor control 2 years after end of treatment

Secondary Outcomes (4)

• late toxicity

  30 days to 2 years after radiochemotherapy

• survival

  2 years after radiochemotherapy

• quality of life EORTC QLQ-C30/HN-35

  regularly up to 2 years after radiochemotherapy

• acute toxicity

  during treatment and up to 30 days after radiochemotherapy

Study Arms (5)

standard radiochemotherapy, hypoxic

OTHER

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

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

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)

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

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.

Radiation: standard radiochemotherapy

Interventions

dose-escalated radiochemotherapy 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.

dose-escalated radiochemotherapy, hypoxic

dose-escalated radiochemotherapy with carbon ion boost 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.

escalated radiochemoth., carbon boost, hypoxic

standard radiochemotherapy 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); standard radiochemotherapy, hypoxic; standard radiochemotherapy, oxic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Technische Universität Dresden: lead

Study Sites (8)

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

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Department of Radiation Oncology Heidelberg University Medical School

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Uniklinikum Wuerzburg

Würzburg, Bavaria, 97080, Germany

Location

Mechthild Krause

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Charité University Hospital

Berlin, 13353, Germany

Location

Ludwig-Maximilian-Universität, Klinikum Großhadern

München, 81377, Germany

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Study Officials

• 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)

  STUDY CHAIR

Central Study Contacts

Mechthild Krause, Prof. Dr.

CONTACT

+49 351 458 2238; mechthild.krause@uniklinikum-dresden.de

Esther Troost, Prof.Dr.Dr.

CONTACT

+49 351 458 7433; esther.troost@uniklinikum-dresden.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Radiotherapy and Radiation Oncology

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: March 6, 2019
• Study Start: July 1, 2024
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 11, 2023

Record last verified: 2023-09

Locations

DE (8)