A Phase III Randomised Control Clinical Trial of Radiotherapy With Radiosensitisation Versus Intravesical Bacillus Calmette-Guerin Therapy for High-risk Non-muscle Invasive Bladder Cancer.

Официальное название

TRAIN - A Phase III Randomised Control Clinical Trial of Radiotherapy With Radiosensitisation Versus Intravesical Bacillus Calmette-Guerin Therapy for High-risk Non-muscle Invasive Bladder Cancer.

Обзор

In the UK 20,000 people develop urothelial bladder cancer each year with 75-80% having Non-Muscle Invasive Bladder Cancer (NMIBC). The current standard of care for patients with High Risk-NMIBC (HR-NMIBC) is either surgery to remove the tumour (transurethral resection of bladder tumour; TURBT) followed by BCG (Bacillus Calmette Guérin, an immunotherapy drug) given directly into the bladder, or surgery to remove the bladder (cystectomy). BCG is given weekly for six weeks followed by maintenance treatment up to 3 years. However, in up to 50% of patients their cancer returns (recurrence) or gets worse (progression) after BCG and 25% stop treatment due to side effects. Globally BCG supply has been restricted in recent years has increased HR-NMIBC recurrence rates and costs. Improved treatments are required, to prevent recurrence, progression and cystectomy, and mitigate the effects of unpredictable supply. Trimodality treatment (TMT) is maximal TURBT + radiotherapy + a radiosensitiser (gemcitabine, mitomycin C/fluorouracil or carbogen/nicotinamide) and is an equivalent alternative treatment to cystectomy for muscle-invasive bladder cancer (MIBC). TMT is not routinely used for HR-NMIBC. A study found that 54% of HR-NMIBC patients who received TMT did not have recurrence within 5 years. Modern radiotherapy is expected to further improve outcomes and minimise side-effects. Patients will be randomised 1:1 to BCG or radiotherapy with radiosensitisation. Patients randomised to the experimental arm will receive 55Gy in 20 fractions. Investigators can then choose from three different options for the radiosensitiser. TRAIN will test if radiotherapy with radiosensitisation improves outcomes for people with HR-NMIBC compared to BCG. TRAIN will recruit 328 patients with HR-NMIBC following maximal TURBT. All patients will be followed up for a minimum of two years to record their response to treatment.

Вмешательства

• Лучевая терапия radiotherapy
  Radiotherapy - 55Gy in 20 fractions treating once daily Monday to Friday over 4 weeks.
• Другое BCG
  BCG protocol of 6 weekly intravesical instillations, followed by 3 weekly instillations at 3, 6, 12, 18, 24, 30, 36 months.

Первичные конечные точки

• To compare event-free survival between BCG and radiotherapy with radiosensitisation. [Срок оценки: From baseline to at least 96 weeks after initial of treatment.]

Вторичные конечные точки (10)

• To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms. [Срок оценки: From baseline to at least 96 weeks post treatment.]
• To evaluate each component of the primary outcome comparing between BCG and radiotherapy with radiosensitisation. [Срок оценки: From baseline to at least 96 weeks post treatment.]
• To establish the tolerability and safety of radiotherapy. [Срок оценки: From baseline to at least end of 4 week treatment.]
• To determine the difference in cancer specific survival between groups. [Срок оценки: From baseline to at least 96 weeks post treatment.]
• To determine the difference in treatment fidelity between the groups. [Срок оценки: From baseline to at least 96 weeks post treatment.]
• To determine the cost-effectiveness of radiotherapy with radiosensitisation compared to BCG. [Срок оценки: From Baseline to at least 96 weeks post treatment.]
• To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms. [Срок оценки: From baseline to at least 96 weeks post treatment.]
• To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms. [Срок оценки: From baseline to at least 96 weeks post treatment.]
• To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms. [Срок оценки: From baseline to at least 96 weeks post treatment.]
• To determine the difference between BCG and radiotherapy in terms of patient-reported symptoms. [Срок оценки: From baseline to at least 96 weeks post treatment.]

Критерии участия

Критерии включения

• Diagnosed with histologically confirmed grade 3 T1 N0 M0 transitional cell carcinoma, OR carcinoma in situ of the bladder (and N0 M0), OR both, with detrusor muscle present in the biopsy specimen if T1 disease (or a repeat resection that does contain muscle that is clear)
• Suitable for BCG treatment
• Suitable for radiotherapy and radiosensitisation according to the schedule of administration outlined in the Radiotherapy Planning Guidance document.
• Life expectancy over 12 months
• ECOG performance status 0 - 2
• Age >=16 years
• Provided written informed consent

Критерии исключения

• MDT selected patients with HR-NMIBC who are deemed best suited for primary cystectomy (patients that have had this treatment recommendation but then decline cystectomy remain eligible for TRAIN)
• Previous radiotherapy to the pelvis
• Previous intravesical therapy
• Poor bladder function (IPSS >16)
• A recent or current other cancer. Current non-melanoma skin cancer, cervical carcinoma in situ or localized prostate cancer not requiring current treatment are permissible, as is a history of a separate other malignancy having completed all active treatment ≥2 years previously and without evidence of relapse
• Pre-existing medical conditions that preclude treatment options in either trial arm
• Patient currently recruited to another interventional trial or participation within an interventional clinical trial within 3 months of the point of registration within TRAIN.
• Pregnant or breast-feeding
• Not able to use appropriate adequate effective contraception during and for 3 months after the study

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

Великобритания · 1 центр

• The Christie — Manchester

Идентификаторы

NCT: NCT07268339 · CFTsp223

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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