Stereotactic Post-operative Radiotherapy for Intraparotid Metastatic Cutaneous Squamous Cell Carcinoma

Обзор

The purpose of this study is to compare the effectiveness and side effects of stereotactic radiotherapy (5 sessions) against conventional (standard) radiotherapy (20-30 sessions) for the treatment of skin cancer involving the head and neck after surgical resection. Stereotactic radiotherapy works in the same way that conventional (standard) radiotherapy does to kill cancer cells by damaging their genetic material and stopping the cancer cells from making copies of themselves. This study will help the study doctors find out if this different approach is the same, better, or worse than the standard of care for your cancer.

Подробное описание

This study is a phase II randomized trial where patients will be randomized in a 1:2 ratio to standard of care treatment with conventional fractionation PORT (Arm 1) vs. ultrahypofractionated stereotactic PORT (Arm 2). Patients will be stratified by pathologic nodal status (pN1 vs. pN2-pN3) per the American Joint Committee on Cancer (AJCC) 8th edition staging and use of immunotherapy (classified as neoadjuvant immunotherapy (with or without adjuvant immunotherapy) vs. planned for adjuvant immunotherapy only vs. no immunotherapy. Patients randomized to Arm 2 will be also compared to historical control data for primary endpoint of tumor local control at 2-years.

The objective of this study is to assess the clinical efficacy, toxicity and QOL of ultra-hypofractionated SABR compared to conventional fractionation for adjuvant radiation following resection of locally advanced, node-positive cutaneous SCC of the head and neck.

Primary endpoint

\- Tumor control within the irradiated field at 2 years following adjuvant radiation completion defined as absence of clinical, radiographic or biopsy-proven recurrence within the irradiated field

Secondary endpoints

* Regional recurrence * Disease-free survival (DFS) * Overall survival (OS) * Rate of salvage treatment (surgery in the ipsilateral neck) and freedom from unsalvageable recurrence in the ipsilateral parotid gland or neck * Radiation-associated toxicity based on the Common Terminology Criteria for Adverse Events(CTCAE) version 5.0 * Patient-reported outcomes using the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) and the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) questionnaires

Вмешательства

• Лучевая терапия SBRT
  Patients will receive ultra-hypofractionated stereotactic radiation over 5 treatments delivered every other weekday or twice weekly as follows: * 40 to 42.5 Gy in 5 fractions: any areas of gross residual disease, or gross PNI on imaging * 32.5 to 35 Gy in 5 fractions: microscopic areas at risk including positive margin and/or ENE * 30 Gy in 5 fractions: entire operative bed including areas of primary tumor and involved nodes and dissected cervical nodal levels * 27.5 to 30 Gy 5 fractions: at ri
• Лучевая терапия Standard Radiation
  Patients will receive daily conventional fractionation radiation over 4 or 6-6.5 weeks based on the treating oncologist's discretion. The below dose levels are recommended in the following clinical scenarios but may be modified per institutional standards: 20-fraction regimen or 30 to 33-fraction regimen

Первичные конечные точки

• Tumor control [Срок оценки: 2 years]

Вторичные конечные точки (7)

• Regional recurrence [Срок оценки: 2 years]
• Disease-free survival (DFS) [Срок оценки: 2 years]
• Overall survival [Срок оценки: 2 years]
• Rate of salvage surgery [Срок оценки: 2 years]
• Radiation-associated toxicity [Срок оценки: Baseline, during treatment, 2 weeks post treatment, 4 weeks post treatment, 3, 12, 18, 24 months post treatment, and yearly from years 2-5 after the end of radiation.]
• Patient-reported outcomes [Срок оценки: Baseline, 3, 6, 12, 18, 24 months post-treatment and yearly from years 2-5 after the end of radiation.]
• Patient Reported Outcome [Срок оценки: Baseline, 3, 6, 12, 18, 24 months post-treatment and yearly from years 2-5 after the end of radiation.]

Критерии участия

Критерии включения

• Age ≥ 18 years
• Patient able to provide informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient is a candidate for curative intent treatment
• Patient is able to comprehend English adequately to complete patient reported outcome questionnaires
• Biopsy-confirmed cutaneous SCC
• Definitive resection of a primary cutaneous tumor within the head and neck
• Tumor stage T1-T4 (AJCC 8th edition); or tumor stage unknown (T0/Tx) with a positive intraparotid, peri-parotid or cervical node that is assumed to be from a head and neck cutaneous SCC by the treating oncologist
• Nodal stage N1-N3 (AJCC 8th edition)
• At least 1 indication for adjuvant radiation, including:

• T3 or T4 tumor stage
• Lymphovascular invasion (LVI)
• Perineural invasion (PNI)
• Positive or close (≤ 3 mm) margin
• ≥ 1 positive intraparotid, peri-parotid or cervical lymph node
• Multiple local recurrences or multi-focal disease
• Neoadjuvant or adjuvant immunotherapy is allowed

Критерии исключения

• Definite metastatic disease at diagnosis
• Pregnant or breastfeeding women
• Significant health conditions or contraindications to receiving surgery and radiation
• History of previous head and neck cancer within 5 years, except for localized skin cancers (i.e. no nodal or distant spread)
• Prior head and neck radiation involving the ipsilateral parotid or neck. However, prior radiation to the index skin cancer that has led to the parotid nodal disease being treated on this trial is allowed, as long as there is no overlap, or inconsequential overlap, in the judgement of the treating oncologist.
• Indications for contralateral neck radiation (i.e. contralateral or bilateral lymph nodes)
• Previous invasive malignancy within 5 years, unless controlled with no evidence of disease

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

Канада · 1 центр

• Verspeeten Family Cancer Centre — London

Публикации

• Culbert M, Bidermann G, Wallace AS. Decisional preferences and satisfaction with short-course radiation for breast cancer. JCO. 2018;36(30_suppl):193-193. doi:10.1200/JCO.2018.36.30_suppl.193
• National Comprehensive Cancer Network Squamous Cell Skin Cancer (version 1.2024). https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed 24 August 2024.
• National Cancer Institute-Common Toxicity Criteria Adverse Events Version 5. Published 2017. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Refer ence_8.5x11.pdf. Accessed 25 August 2024.
• Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. PMID 18929686
• Hatswell A, Freemantle N, Baio G, Lesaffre E, van Rosmalen J. Summarising salient information on historical controls: A structured assessment of validity and comparability across studies. Clin Trials. 2020 Dec;17(6):607-616. doi: 10.1177/1740774520944855. Epub 2020 Sep 21. PMID 32957804
• Pocock SJ. The combination of randomized and historical controls in clinical trials. J Chronic Dis. 1976 Mar;29(3):175-88. doi: 10.1016/0021-9681(76)90044-8. No abstract available. PMID 770493
• Ringash J, O'Sullivan B, Bezjak A, Redelmeier DA. Interpreting clinically significant changes in patient-reported outcomes. Cancer. 2007 Jul 1;110(1):196-202. doi: 10.1002/cncr.22799. PMID 17546575
• Yao JJ, Zhou GQ, Jin YN, Zhang WJ, Lin L, Yu XL, Shao JY, Ma J, Sun Y. Predictors of Mastoiditis after Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma: A Dose-Volume Analysis. J Cancer. 2016 Jan 8;7(3):276-82. doi: 10.7150/jca.13183. eCollection 2016. PMID 26918040

Идентификаторы

NCT: NCT07337161 · 5201 · 15521

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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