International Penile Advanced Cancer Trial (International Rare Cancers Initiative Study)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 200
- 试验地点
- 34
- 主要终点
- Overall survival
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Measurable disease as determined by RECIST (version 1.1) criteria;
- •Histologically-proven squamous cell carcinoma of the penis,
- •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.
排除标准
- •Pure verrucous carcinoma of the penis,
- •Nonsquamous malignancy of the penis,
- •Squamous carcinoma of the urethra,
- •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.
研究组 & 干预措施
Arm A - Standard Surgery (ILND)
Part of randomisation 1.
The total treatment duration (Inguinal Lymph Node Dissection (ILND)) is estimated to be over 1 day for those patients allocated to Arm A - standard surgery.
干预措施: ILND - Inguinal Lymph Node Dissection (Procedure)
Arm C - neoadjuvant chemoradiotherapy
Part of randomisation 1.
Radiotherapy dose is 45Gy in 25 fractions over 5 weeks using 6-10 MV photons to all regions.
Concurrent cisplatin 40mg/m2 will be given weekly, subject to GFR>45mls/min.
干预措施: Cisplatin (Drug)
Arm C - neoadjuvant chemoradiotherapy
Part of randomisation 1.
Radiotherapy dose is 45Gy in 25 fractions over 5 weeks using 6-10 MV photons to all regions.
Concurrent cisplatin 40mg/m2 will be given weekly, subject to GFR>45mls/min.
干预措施: Intensity modulated radiation treatment (IMRT) (Radiation)
Arm Q - Surveillance no prophylactic PLND
no prophylactic PLND Part of randomisation 2.
For patients who have NOT received neoadjuvant chemoradiotherapy:
Groin: One or both groins may be boosted up to 54Gy in 25 fractions. An IMRT boost of up to 57 Gy can be given to recurrent or residual macroscopic tumour
Pelvis: the dose is limited to 45Gy unless IMRT is available. An IMRT boost of up to 54Gy in 25 fractions is applied to:
Any macroscopic tumour or pathological lymph nodes Electively to external iliac nodes in patient with high disease burden
Arm P - prophylactic PLND
Part of randomisation 2.
Prophylactic pelvic lymph node dissection (PLND) - The total treatment duration is estimated to be over 1 day.
Patients who have NOT received neoadjuvant chemoradiotherapy will receive adjuvant chemoradiotherapy:
Cisplatin 40mg/m2 will be given weekly, subject to GFR>45mls/min.
Groin: One or both groins may be boosted up to 54Gy in 25 fractions. An IMRT boost of up to 57 Gy can be given to recurrent or residual macroscopic tumour
Pelvis: the dose is limited to 45Gy unless IMRT is available. An IMRT boost of up to 54Gy in 25 fractions is applied to:
- Any macroscopic tumour or pathological lymph nodes
- Electively to external iliac nodes in patient with high disease burden
Patients who have had neoadjuvant chemoradiotherapy will have prophylactic PLND alone.
干预措施: Prophylactic PLND - pelvic lymph node dissection (Procedure)
Arm B - neoadjuvant chemotherapy
Part of randomisation 1.
Patients will receive up to 4 cycles of Paclitaxel, Ifosfamide, and Cisplatin (TIP).
Administration on an outpatient basis:
Paclitaxel 175 mg/m2, day 1, Ifosfamide 900 mg/m2, days 2-5, Cisplatin 15 mg/m2, days 1-5
Administration on an inpatient basis:
Paclitaxel 175 mg/m2, day 1, Ifosfamide 1200 mg/m2, days 1-3, Cisplatin 25 mg/m2, days 1-3
干预措施: Paclitaxel (Drug)
Arm B - neoadjuvant chemotherapy
Part of randomisation 1.
Patients will receive up to 4 cycles of Paclitaxel, Ifosfamide, and Cisplatin (TIP).
Administration on an outpatient basis:
Paclitaxel 175 mg/m2, day 1, Ifosfamide 900 mg/m2, days 2-5, Cisplatin 15 mg/m2, days 1-5
Administration on an inpatient basis:
Paclitaxel 175 mg/m2, day 1, Ifosfamide 1200 mg/m2, days 1-3, Cisplatin 25 mg/m2, days 1-3
干预措施: Ifosfamide (Drug)
Arm B - neoadjuvant chemotherapy
Part of randomisation 1.
Patients will receive up to 4 cycles of Paclitaxel, Ifosfamide, and Cisplatin (TIP).
Administration on an outpatient basis:
Paclitaxel 175 mg/m2, day 1, Ifosfamide 900 mg/m2, days 2-5, Cisplatin 15 mg/m2, days 1-5
Administration on an inpatient basis:
Paclitaxel 175 mg/m2, day 1, Ifosfamide 1200 mg/m2, days 1-3, Cisplatin 25 mg/m2, days 1-3
干预措施: Cisplatin (Drug)
结局指标
主要结局
Overall survival
时间窗: up to 5 years
The primary outcome measure that will be measured for all trial patients is survival time. This is defined in whole days as the time from the date of randomisation to the date of death from any cause; for those who have not been reported as dead at the time of analysis, the survival time will be censored at the date of last follow-up.
次要结局
- Operability(2-6 weeks)
- Occurrence of Lower limb/scrotal oedema(up to 5 years)
- Disease specific survival time(up to 5 years)
- Number of patients experience a grade 3 or 4 toxicity(up to 5 years)
- Disease-free survival time(up to 5 years)
- Occurrence of surgical complication(up to 5 years)
- Is it possible to achieve pathological nodal assessment after chemotherapy(12 weeks)
- Quality of life(Baseline, 3, 6, 9, 12, 18, 24 and 36 months)
- Occurrence of Pathological complete remission(Time to complete remission after randomisation)
- On-schedule delivery of neoadjuvant therapy(After randomisation up to 12 weeks)