Contact Radiotherapy for Rectal Cancer

Официальное название

Contact Radiotherapy for Rectal Cancer (CORRECT): a Multicenter Randomized Phase II Trial

Обзор

The aim of the CORRECT phase 2 study is to show non-inferiority of Contact x-ray brachytherapy (CXB) + short-course radiotherapy (SCRT) compared to the experimental arm of the OPERA trial in organ preservation for early and early intermediate rectal cancer (cT1-3abN1).

Подробное описание

The primary aim of this study is to determine whether a combination of CXB + SCRT is non-inferior to CXB + chemoradiotherapy (CRT) regarding the primary endpoint 2-year organ preservation rate. Additionally, we hypothesize that a chemotherapy-free, radiation-only experimental treatment CXB+SCRT is associated with less side-effects compared to the OPERA regime.

In the OPERA trial (Gerard et al, 2023), the CXB was delivered in combination with long-course CRT. A combination of short-course radiotherapy (SCRT) and CXB has previously been used mainly in elderly and comorbid patients not suitable for long-course chemoradiotherapy. Recently, an international multi-institution report showed good outcomes of planned organ preservation using SCRT together with contact brachytherapy boost. However, no randomized data on this combination therapy are available. There are further no trials comparing CRT+CXB and SCRT+CXB.

Study participants will be randomized to either the standard treatment consisting of CXB (90Gy/3 fractions/4 weeks) and CRT 45/50 Gy (1.8/2 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (900 mg/m2 bid, on radiation days) OR the experimental treatment consisting of CXB (90Gy/3 fractions/4 weeks) SCRT (25 Gy in 5 daily fractions over a total time of 1 week, treating 5 days per week, 1 fraction per day, using 5 Gy per fraction, over the maximum treatment period of eight calendar days).

Вмешательства

• Лучевая терапия Radiotherapy
  45/50 Gy (1.8/2 Gy/fraction/5 weeks)
• Лучевая терапия Short-course radiotherapy
  25 Gy in 5 daily fractions over a total time of 1 week, treating 5 days per week, 1 fraction per day, using 5 Gy per fraction, over the maximum treatment period of eight calendar days
• Лучевая терапия Contact x-ray brachytherapy
  90Gy/3 fractions/4 weeks
• Препарат Chemotherapy
  Capecitabine (900 mg/m2 bid, on radiation days)

Первичные конечные точки

• Rectum preservation [Срок оценки: At 24 months after start of treatment]

Вторичные конечные точки (12)

• Acute treatment-related toxicity [Срок оценки: From start of treatment until 90 days after ending treatment]
• Late treatment related toxicity [Срок оценки: From 90 days after ending treatment until end of study]
• Clinical complete response (cCR) [Срок оценки: At 14-16 and 24-26 weeks after start of treatment]
• Postoperative complications [Срок оценки: Within the first 30 days after Total Mesorectal Excision (TME) surgery]
• Stoma [Срок оценки: At 12 and 24 months after start of treatment]
• Metastasis-free survival [Срок оценки: At 24 months after start of treatment]
• Locoregional failure [Срок оценки: At 24 months after start of treatment]
• Overall survival [Срок оценки: At 24 months after start of treatment]
• TME-free survival [Срок оценки: At 24 months after start of treatment]
• Salvage TME resections [Срок оценки: From 24 weeks after start of treatment until end of study]
• Tumor regression grade [Срок оценки: After 14-16 weeks and 24-26 weeks after start of treatment]
• Sphincter preservation [Срок оценки: At 24 months after start of treatment]

Критерии участия

Критерии включения

• Adenocarcinoma of the rectum classified as:
• cT1-cT3ab, < 5 cm largest diameter and < ½ circumference (MRI staging), N0-N1 (<= 3 nodes < 8mm diameter), M0
• Performance status (ECOG) 0-1
• Operable patient
• Tumor accessible to endocavitary contact X-ray brachytherapy with a distance from the lower tumor border to the anal verge ≤10 cm
• 18 years or above
• No comorbidity preventing treatment
• Patient having read the information note and having signed the informed consent
• Follow-up possible

Критерии исключения

• Inoperable patient
• T3cd, T4, T≥ 5cm, Involvement of more than half of the bowel circumference
• Distance from the lower tumor border to the anal verge >10 cm
• N2-status at diagnosis or N1 with any node>= 8 mm diameter
• Patient presenting with metastasis at diagnosis (M1)
• Previous pelvic irradiation
• Tumor with extramural vascular invasion
• Poorly differentiated tumor
• Simultaneous progressive cancer
• Tumor invading external anal sphincter or growth within 1 mm of the levator
• Tumor within 1 mm from MRF (mesorectal fascia)
• Patient unable to receive CXB or CRT
• Any significant concurrent medical illness that in the opinion of the investigator would preclude protocol therapy
• Patient with history of poor compliance or current or past psychiatric conditions or severe acute or chronic medical conditions that would interfere with the ability to comply with the study protocol
• Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
• Total DPD deficiency

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 · 2 центра

• Karolinska University Hospital, Theme Cancer, Dept of Pelvic cancer — Stockholm
• Uppsala University Hospital, Colorectal Surgery — Uppsala

Публикации

• Gerard JP, Barbet N, Schiappa R, Magne N, Martel I, Mineur L, Deberne M, Zilli T, Dhadda A, Myint AS; ICONE group. Neoadjuvant chemoradiotherapy with radiation dose escalation with contact x-ray brachytherapy boost or external beam radiotherapy boost for organ preservation in early cT2-cT3 rectal adenocarcinoma (OPERA): a phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Apr PMID 36801007
• Nilsson PJ, Folkesson J, Marsk R, Radu C, Stratulat I, Blomqvist L, Martling A, Valdman A. Contact radiotherapy for rectal cancer (CORRECT): study protocol for a multicentre randomised phase II trial. BMJ Open. 2025 Apr 9;15(4):e100356. doi: 10.1136/bmjopen-2025-100356. PMID 40204311

Идентификаторы

NCT: NCT06501053 · CORRECT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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