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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Лучевая терапия 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(RB
• Лучевая терапия 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.
• Лучевая терапия 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.

Первичные конечные точки

• local tumour control [Срок оценки: Local tumor control 2 years after end of treatment]

Вторичные конечные точки (4)

• late toxicity [Срок оценки: 30 days to 2 years after radiochemotherapy]
• survival [Срок оценки: 2 years after radiochemotherapy]
• quality of life EORTC QLQ-C30/HN-35 [Срок оценки: regularly up to 2 years after radiochemotherapy]
• acute toxicity [Срок оценки: during treatment and up to 30 days after radiochemotherapy]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 8 центров

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

Идентификаторы

NCT: NCT03865277 · STR-INDIRA-MISO-2014

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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