International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study)

Обзор

This is an international phase III trial, with a Bayesian design, incorporating two sequential randomisations. It efficiently examines a series of questions that routinely arise in the sequencing of treatment. The study design has evolved from lengthy international consultation that has enabled us to build consensus over which questions arise from current knowledge and practice. It will enable potential randomisation for the majority of patients with inguinal lymph node metastases and will provide data to inform future clinical decisions. InPACT-neoadjuvant patients are stratified by disease burden as assessed by radiological criteria. Treatment options are then defined according to the disease burden strata. Treatment is allocated by randomisation. Patients may be allocated to one of three initial treatments: A. standard surgery (ILND); B. neoadjuvant chemotherapy followed by standard surgery (ILND); or C. neoadjuvant chemoradiotherapy followed by standard surgery (ILND). After ILND, patients are defined as being at low or high risk of recurrence based on histological interpretation of the ILND specimen. Patients at high risk of relapse are eligible for InPACT-pelvis, where they are randomised to either: P. prophylactic PLND Q. no prophylactic PLND

Вмешательства

• Процедура ILND - Inguinal Lymph Node Dissection
  Surgery to remove the lymph nodes in the groin near to where the cancer first appeared.
• Препарат Paclitaxel
  Dose 175mg/m2 as part of TIP regimen.
• Препарат Ifosfamide
  Dose 900mg/m2 as part of TIP regimen.
• Препарат Cisplatin
  Dose 15mg/m2 as part of TIP regimen (neoadjuvant chemotherapy arm) Dose 40mg/m2 for use concurrently with raditotherapy (chemoradiotherapy arm)
• Лучевая терапия Intensity modulated radiation treatment (IMRT)
  Treatment with very high energy X-rays (radiotherapy).
• Процедура Prophylactic PLND - pelvic lymph node dissection
  Surgery to remove the lymph nodes deeper in the pelvis, further away from where the cancer first appeared, that are at high risk of harbouring cancer.

Первичные конечные точки

• Overall survival [Срок оценки: up to 5 years]

Вторичные конечные точки (10)

• Disease specific survival time [Срок оценки: up to 5 years]
• Number of patients experience a grade 3 or 4 toxicity [Срок оценки: up to 5 years]
• Disease-free survival time [Срок оценки: up to 5 years]
• Occurrence of surgical complication [Срок оценки: up to 5 years]
• Is it possible to achieve pathological nodal assessment after chemotherapy [Срок оценки: 12 weeks]
• Quality of life [Срок оценки: Baseline, 3, 6, 9, 12, 18, 24 and 36 months]
• Occurrence of Pathological complete remission [Срок оценки: Time to complete remission after randomisation]
• Operability [Срок оценки: 2-6 weeks]
• Occurrence of Lower limb/scrotal oedema [Срок оценки: up to 5 years]
• On-schedule delivery of neoadjuvant therapy [Срок оценки: After randomisation up to 12 weeks]

Критерии участия

Критерии включения

• Written informed consent
• Measurable disease as determined by RECIST (version 1.1) criteria;
• Histologically-proven squamous cell carcinoma of the penis,
• Stage:

• any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node), M0 or;
• any T, N2 (i.e. palpable mobile multiple or bilateral inguinal lymph nodes), M0 or;
• any T, N3 (i.e. fixed inguinal nodal mass or any pelvic lymphadenopathy), M0
• Performance Status ECOG 0, 1 or 2.

Критерии исключения

• Pure verrucous carcinoma of the penis,
• Nonsquamous malignancy of the penis,
• Squamous carcinoma of the urethra,
• Stage M1,
• Previous chemotherapy or chemoradiotherapy,
• Concurrent malignancy (other than SCC or Basal Cell Carcinoma of non-penile skin) that has required surgical or non-surgical treatment in the last 3 years.

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

США · 11 центров

• Los Angeles County-USC Medical Center — Los Angeles
• USC / Norris Comprehensive Cancer Center — Los Angeles
• Moffitt Cancer Center — Tampa
• Grady Health System — Atlanta
• Emory University Hospital/Winship Cancer Institute — Atlanta
• University of Chicago Comprehensive Cancer Center — Chicago
• Mayo Clinic — Rochester
• Ohio State University Comprehensive Cancer Center — Columbus
• … и ещё 3 центра

Великобритания · 6 центров

• Velindre NHS Trust — Cardiff
• University Hospitals of Leicester NHS Trust — Leicester
• The Royal Marsden NHS Foundation Trust — London
• St George's Hospital NHS Foundation Trust — London
• Norfolk and Norwich University Hospitals NHS Foundation Trust — Norwich
• Swansea Bay University Health Board — Swansea

Идентификаторы

NCT: NCT02305654 · ICR CTSU/2014/10048 · CRUK/13/005 · 13580965 · EA8134 · IRCI004 · 2015-001199-23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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