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

Head and Neck Squamous Cell Carcinoma Clinical Trial

— INDIRA-MISO  

Official title:

Individualized Radiation Dose Prescription in HNSCC Based on F-MISO-PET Hypoxia-Imaging: Multi-center, Randomized Phase-II-trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03865277
• Other study ID #: STR-INDIRA-MISO-2014
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2024
• Est. completion date: September 30, 2027

Study information

• Verified date: September 2023
• Source: Technische Universität Dresden
• Contact: Mechthild Krause, Prof. Dr.
• Phone: +49 351 458 2238
• Email: mechthild.krause[@]uniklinikum-dresden.de
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 276
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Squamous Cell Carcinoma
• Hypoxia
• Squamous Cell Carcinoma of Head and Neck

Intervention

Radiation:
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Germany	Charité University Hospital	Berlin
Germany	Mechthild Krause	Dresden	Saxony
Germany	Medical Faculty, Albert-Ludwigs-Universität Freiburg, Department of Radiation Oncology	Freiburg	Baden-Wuerttemberg
Germany	Department of Radiation Oncology Heidelberg University Medical School	Heidelberg	Baden-Wuerttemberg
Germany	Universitätsklinikum Leipzig	Leipzig	Saxony
Germany	Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie	Mannheim	Baden-Wuerttemberg
Germany	Ludwig-Maximilian-Universität, Klinikum Großhadern	München
Germany	Uniklinikum Wuerzburg	Würzburg	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität Dresden

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	late toxicity	late toxicity based on CTCAE 5.0	30 days to 2 years after radiochemotherapy
Secondary	survival	Overall survival	2 years after radiochemotherapy
Secondary	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)	regularly up to 2 years after radiochemotherapy
Secondary	acute toxicity	acute toxicity based on CTCAE 5.0	during treatment and up to 30 days after radiochemotherapy