Chemoradiotherapy Followed by Planned Surgery or by Surveillance and Surgery Only When Needed for Oesophageal Cancer

Официальное название

NEoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed (NEEDS Trial)

Обзор

NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the first co-primary endpoint overall survival and superiority for the experimental intervention definitive chemoradiotherapy. A second co-primary endpoint is global health related quality of life (HRQOL) one year after randomisation. A third co-primary endpoint is eating restictions one year after randomisation. The aim is to compare outcomes after neoadjuvant chemoradiotherapy with subsequent esophagectomy to definitive chemoradiotherapy with surveillance and salvage esophagectomy as needed in patients with resectable locally advanced squamous cell carcinoma (SCC) of the esophagus, with the aim to provide generalisable guidance for future clinical practice.

Вмешательства

• Лучевая терапия Neoadjuvant radiotherapy (arm A)
  1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
• Препарат Carboplatin, paclitaxel
  Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy
• Процедура Esophagectomy
  Esophagectomy performed within 8 weeks after termination of chemoradiotherapy
• Лучевая терапия Neoadjuvant radiotherapy (arm B)
  Two alternative schemes: 1. 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy. 2. 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
• Препарат Carboplatin, paclitaxel
  Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy (5 weeks or 6 weeks, depending on the radiotherapy regimen used).
• Препарат Cisplatin, paclitaxel
  Cisplatin 75mg/m2 on the first day of weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion on the first four days of weeks 1 and 5.
• Препарат Oxaliplatin, calcium folinate, 5-fluorouracil
  FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 on the first days of weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion on the first two days of weeks 1, 3 and 5.
• Процедура Esophagectomy
  Esophagectomy only in case of residual or recurrent locoregional cancer.

Первичные конечные точки

• Overall survival [Срок оценки: 3 years after randomisation]
• Global Health-related quality of life (HRQOL) [Срок оценки: 1 year after randomisation]
• Eating restrictions [Срок оценки: 1 year after randomisation]

Вторичные конечные точки (12)

• Health related quality of life of Cancer patients [Срок оценки: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation]
• Health related quality of life, oesophageal specific. [Срок оценки: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation]
• Health related quality of life, general health [Срок оценки: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation]
• Event-free survival [Срок оценки: 5 years after randomisation]
• Loco-regional and distant relapse rates [Срок оценки: 5 years after randomisation]
• Histopathological response according to Mandard in operated patients [Срок оценки: 5 years after randomisation]
• Health economy [Срок оценки: At baseline and 6, 12, 24, 36 and 60 months after randomisation]
• Surgical complications [Срок оценки: After surgery in operated patients, up to 5 years after randomisation]
• Treatment-related adverse events and toxicity [Срок оценки: Up to 5 years after randomisation]
• Nutritional outcomes - weight [Срок оценки: Up to 5 years after randomisation]
• Nutritional outcomes - dysphagia [Срок оценки: Up to 5 years after randomisation]
• Gender stratified analyses of all endpoints [Срок оценки: Up to 5 years after randomisation]

Критерии участия

Критерии включения

• Histopathologically confirmed SCC of the esophagus in locally advanced stages cT1 N+ or cT2-4a any N, M0, according to current (8th) version of of the AJCC TNM classification.
• Technically resectable disease according to the local multidisciplinary team conference (MDT)/tumor board.
• Performance status ECOG 0-1.
• Adequate organ function.
• Women of childbearing potential (WOCBP\*) must have a negative serum or urine pregnancy test.
• Patients of childbearing/reproductive potential should use highly effective method of birth control measures during the study treatment period and for at least five months after the last study treatment.
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP/GDPR and national/local regulations.

Критерии исключения

• M1 according to current (8th) version of of the AJCC TNM classification.
• cT4b according to current (8th) version of of the AJCC TNM classification.
• Primary tumor not resectable without laryngectomy.
• Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the eligibility of the patient for multimodality treatment with chemoradiotherapy followed by esophagectomy.
• Subjects not considered likely to tolerate multimodality treatment with chemoradiotherapy followed by esophagectomy.
• Subjects with previous malignancies are excluded unless a complete remission or complete resection was achieved at least 5 years prior to study entry.
• Prior or concomitant treatment with radiotherapy or chemoradiotherapy with potential overlap of radiotherapy fields.
• Known uncontrollable hypersensitivity to the components of the chemotherapeutic agents used in the trial regimens.
• Inability to fully understand and digest study patient information or to comply with study instructions due to language difficulty or cognitive failure such as dementia or severe psychiatric disorder.

(Criteria slightly shortened)

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

Швеция · 6 центров

• Linköpings universitetssjukhus — Linköping
• Skånes universitetssjukhus — Lund
• Örebro universitetssjukhus — Örebro
• Karolinska University Hospital — Stockholm
• Norrlands universitetssjukhus — Umeå
• Akademiska sjukhuset — Uppsala

Норвегия · 3 центра

• Oslo universitetssykehus — Oslo
• Universitetssykehuset Nord-Norge — Tromsø
• St Olavs Hospital — Trondheim

Канада · 1 центр

• McGill University Health Centre — Montreal

Ирландия · 1 центр

• Cancer Clinical Trials Unit (CCTU) at St. James's Hospital — Dublin

Тайвань · 1 центр

• Chang Gung Memorial Hospital — Linkou District

Публикации

• Nilsson M, Olafsdottir H, Alexandersson von Dobeln G, Villegas F, Gagliardi G, Hellstrom M, Wang QL, Johansson H, Gebski V, Hedberg J, Klevebro F, Markar S, Smyth E, Lagergren P, Al-Haidari G, Rekstad LC, Aahlin EK, Wallner B, Edholm D, Johansson J, Szabo E, Reynolds JV, Pramesh CS, Mummudi N, Joshi A, Ferri L, Wong RK, O'Callaghan C, Lukovic J, Chan KK, Leong T, Barbour A, Smithers M, Li Y, Kang PMID 35912196

Идентификаторы

NCT: NCT04460352 · NEEDS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗