DP-IMRT Pancreas: A Non-randomised Phase I/II Study of Dose-escalated Hypofractionated Dose-Painted Intensity Modulated Radiotherapy (DPIMRT) in Resectable/Borderline Resectable Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 49
- 试验地点
- 2
- 主要终点
- Phase 2 - to determine the frequency and severity of DLTs due to AE/Toxicity meeting definition of DLT at 4 weeks post RT
研究概览
简要总结
This is a prospective non-randomised Phase I/II Radiotherapy (RT) study with patients recruited to escalated dose cohorts. Patients with resectable or borderline resectable (per the National Comprehensive Cancer Network (NCCN) criteria) pancreatic adenocarcinoma will receive dose-escalated hypofractionated DP-IMRT via Intensity Modulated Radiotherapy (IMRT) / Volume Modulated Arc Therapy (VMAT).
详细描述
The study treatment is radiotherapy. Different doses of radiotherapy will be given to patients. The first group of patients will receive the lowest dose (dose level 1) (this is the dose delivered to patients as standard of care). If the treatment does not cause serious side effects, it will be given to the next group of patients enrolled at a higher dose (dose level 2) (this is called 'dose escalation'). If this higher dose of treatment does not cause serious side effects, the next group of patients will receive a higher dose (dose level 3). The doses will continue to increase for every group of patients, as long as no serious side effects occur. If this happens, the study is halted. Once the optimum dose level has been reached, a larger cohort of patients will all receive this dose.
Phase I: A 3+3 dose escalation design is proposed to determine the maximum tolerated dose (MTD) defined by the number of radiotherapy-related ≥ Grade 3 acute toxicities assessed up to 4 weeks post RT. Three cohorts of between 3 and 6 patients at each dose level will be accrued in order to establish the MTD (minimum of 6, maximum of 18 patients). The MTD defined in Phase I will be the dose which will be used in Phase II of the trial. Phase II: 49 patients: Once the MTD is established, patients will continue to be recruited at that dose level up to a total of 49 patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is a prospective non-randomised Phase I/II Radiotherapy (RT) study with patients recruited to escalated dose cohorts. Patients with resectable or borderline resectable (per the National Comprehensive Cancer Network (NCCN) criteria) pancreatic adenocarcinoma will receive dose-escalated hypofractionated DP-IMRT via Intensity Modulated Radiotherapy (IMRT) / Volume Modulated Arc Therapy (VMAT).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained prior to any study-related procedures
- •Age ≥18 years
- •ECOG (European Cooperative Oncology Group) performance status (PS) 0-2
- •Resectable or borderline resectable per National Comprehensive Cancer Network (NCCN) criteria (see Appendix H)
- •Patients with histologically confirmed Pancreatic Ductal Adenocarcinoma (PDAC), with the following staging: cT1N0-2, cT2N0-2, cT3N0-2 [American Joint Committee on Cancer (AJCC) 8th edition] (see Appendix C) who are planned for pre-operative systemic chemo-radiotherapy
- •Imaging with Computed Tomography Thorax Abdomen and Pelvis (CT TAP) and Magnetic resonance imaging (MRI) Abdomen confirms no evidence of metastatic disease
- •Females of child-bearing potential (see Appendix G) must not be pregnant (or lactating) and must be prepared to use adequate contraception methods during treatment. Males whose female partners are of child-bearing potential must be prepared to use adequate contraception methods during treatment.
排除标准
- •Previous thoracic or abdominal or pelvic radiation therapy (RT)
- •Previous treatment for bilirubin regression, other than stenting
- •Known co-existing or prior malignancy within the last 5 years (except for Basal Cell Carcinoma (BCC) or Squamous Cell Carcinoma (SCC) of the skin) which is likely to interfere with treatment or assessment of outcomes
- •Syndromes or conditions associated with increased radiosensitivity
- •Uncontrolled intercurrent illness that is likely to interfere with treatment or assessment of outcomes, or psychiatric illness/ social situations that would limit compliance with study requirements
- •Evidence of any other significant clinical disorder or laboratory findings that makes it undesirable for the patient to participate in the study, or if it is felt by the research/ Medical team that the patient may not be able to comply with the protocol and follow up schedule due to psychological, familial, sociological or geographical conditions
研究组 & 干预措施
Radiation; IMRT
Fifteen fractions of external beam radiation therapy (EBRT) delivered via IMRT/ VMAT. Cohort 1 (n = 3-6) Single PTV 40.05 Gy/15#, homogenous dose* Cohort 2 (n = 3-6) High Risk PTV 45 Gy/15# SIB to PTV tumour, Elective PTV 40.05 Gy/15# to nodal regions* Cohort 3 (n = 3-6) High risk PTV 48 Gy/15# SIB to PTV tumour, Elective PTV 40.05 Gy/15# to nodal regions
* Progression to the next dose in successive cohorts depends on the number of patients experiencing DLTs within 4 weeks post-RT treatment in each patient cohort.
干预措施: Dose-Painted Intensity Modulated Radiotherapy (Radiation)
结局指标
主要结局
Phase 2 - to determine the frequency and severity of DLTs due to AE/Toxicity meeting definition of DLT at 4 weeks post RT
时间窗: 4 weeks
The rate of DLTs up to 4 weeks post RT will be calculated. This proportion along with the 90% confidence intervals will be reported.
Phase 1 - to establish the MTD in a dose-escalated and hypofractionated RT regime delivered via IMRT/VMAT by the number of DLTs
时间窗: 4 weeks
To establish the MTD in a dose-escalated and hypofractionated RT regime delivered via IMRT/VMAT by the number of DLTs, and the rate of patient withdrawal from trial treatment due to DLTs. Analysis will be performed for each cohort after all patients have been assessed for their 4-week post RT assessment.
Phase 2 - to determine the rate of patient withdrawal from trial treatment due to AE/Toxicity meeting definition of DLT at 4 weeks post RT
时间窗: 4 weeks
The rate of withdrawal from trial treatment of patients due to DLTs will be calculated. This proportion along with the 90% Confidence Interval will be reported. Other toxicity data including SAEs will be summarised and presented in tabular format with proportions plus 95% Confidence Interval where appropriate.
次要结局
- To evaluate Quality of Life(2 years)
- To document the proportion of peri-operative complications(2 years)
- To quantify the percentage of histologically proven R0 resections in the trial patient group (R0 to be defined as a minimal clearance of at least1 mm).(2 years)
- To determine the rate of failure to progress to surgery due to disease progression during neoadjuvant radiotherapy, and conversely the proportion of patients who do receive surgical resection(2 years)
- To evaluate the impact of treatment on OS, overall and by resectability (whether resectable or borderline resectable)(2 years)
- To evaluate the impact of treatment on PFS, overall and by resectability (whether resectable or borderline resectable)(2 years)
- To evaluate tumour response on surgically resected patients using resected specimens(2 years)
- To evaluate the incidence of late GI toxicities in patients who do not undergo surgical resection(2 years)