INTENSE: A Phase I/II Study of INhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- To assess the safe delivery of an achievable level of dose escalation in a dose escalated and intensified RT regime delivered via VMAT/IMRT and focused on the GTV by the proportion of grade ≥3 toxicities determined to be related to RT
研究概览
简要总结
This is a prospective non-randomised Phase I/II study with patients recruited to escalated dose cohorts. Escalated dose to the iGTV (internal gross tumour volume), with 60 Gy to the conventional PTV (planning target volume), will be delivered to successive cohorts of participants (6-12 participants/cohort) until the maximum tolerated oesophageal dose is determined. The minimum dose will be 60 Gy delivered via intensity modulated radiation therapy (IMRT) or volume modulated arc therapy (VMAT), planned on an Average Intensity Projection (AVIP) dataset.
Standard of care chemotherapy.
There will be two treatment arms; one with patients who are planned to receive neo-adjuvant or no chemotherapy, and the other with patients who are planned to receive concurrent chemotherapy.
详细描述
This is a prospective non-randomised Phase I/II cohort study; please see above for Radiation Therapy and Chemotherapy treatment details
Each cohort will require a minimum of 6 and a maximum of 12 patients. Once 6 patients have been treated in a cohort a two-month break is taken before toxicity is analysed.
- If 2 or fewer patients experience a grade ≥3 toxicity, the next cohort will be enrolled and will receive an escalated dose (an additional +5 Gy at each escalation up to a maximum of 75 Gy)
- If 3 of the 6 patients experience a grade ≥3 toxicity, a further 6 patients will be recruited into that dose level
- If 4 or more patients experience a grade ≥3 toxicity then the MTD is fixed at the dose level of the previous cohort
If the cohort is extended to 12 patients, the following rules apply:
- If 4 or fewer patients experience a grade ≥3 toxicity, the next cohort will be enrolled and will receive an escalated dose.
- If 5 of the 12 patients experience a grade ≥3 toxicity, then the MTD is fixed at that dose level and recruitment continues up to a total of 24 patients at that dose level.
- If 6 or more patients experience a grade ≥3 toxicity, then the MTD is fixed at the dose level of the previous cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •18 years of age
- •ECOG (European Cooperative Oncology Group) performance status 0-2 (0-1 for concurrent chemotherapy)
- •Weight loss <10% within 3 months of diagnosis
- •Histological diagnosis (biopsy or cytology) of NSCLC (Squamous Cell Carcinoma (SCC), Adenocarcinoma, Large Cell).
- •Eligible NSCLC stages: IIA (provided N1); IIB (including T3N0 if unresectable or unsuitable for stereotactic ablative body radiation therapy (SABR)); IIIA and IIIB
- •Inoperable (as per Multi-Disciplinary Team (MDT)) or patient refuses surgery
- •Respiratory function:
- •Forced Expiratory Volume (FEV1) ≥ 1L or ≥ 40% of predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) ≥ 40%
- •Radiological confirmation of disease via a Positron Emission Tomography (PET) scan prior to registration.
- •Life expectancy, from causes other than lung cancer, of greater than 12 months (as per physician's opinion)
- •Females of child bearing potential (see Appendix H) must not be pregnant 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. Examples of effective contraception methods are a condom or a diaphragm with spermicidal jelly, or oral, injectable or implanted birth control.
- •Provision of written consent in line with ICH-GCP guidelines
排除标准
- •Previous thoracic radiation therapy
- •Known co-existing or prior malignancy which is likely to interfere with treatment or assessment of outcomes
- •Known distant metastases or metastatic pleural effusion
- •Pancoast tumours (tumour of the pulmonary apex)
- •Supraclavicular nodal involvement
- •Spinal cord involvement
- •Patients with syndromes or conditions associated with increased radiosensitivity or development of lung fibrosis
- •Suitable for SABR
- •Idiopathic pulmonary fibrosis/usual interstitial pneumonia
- •Uncontrolled intercurrent illness that is likely to interfere with treatment or assessment of outcomes
- •Psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or lactating at the time of proposed randomisation
- •Evidence of any other significant clinical disorder or laboratory finding 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
研究组 & 干预措施
Trial Cohort Description
Escalated dose of min 65Gy to the iGTV, with 60Gy to PTV delivered to successive cohorts of patients(pts) until the MTD oesophageal dose is determined. Toxicity will be analysed 2 months post 6pts treated in a cohort.
If: ≤2pts have ≥G3 toxicity, next cohort will be enrolled & receive escalated dose (an additional +5Gy at each escalation upto max 75Gy)/3 of 6pts have ≥G3 toxicity, a further 6pts will be recruited into that dose level/≥4pts have ≥G3 toxicity, the MTD is fixed at dose level of previous cohort
Cohort is extended to 12pts:
If: ≤4pts have ≥G3 toxicity, next cohort will be enrolled & receive escalated dose/5 of 12pts have ≥G3 toxicity, the MTD is fixed at that dose level & recruitment continues up to 24pts/≥6pts have ≥G3 toxicity, the MTD is fixed at the dose level of previous cohort.
Once the max dose cohort is established, recruiting will continue at that dose until 24pts. Concurrent & neo-adjuvant/no chemotherapy arms will be escalated independently of each other
干预措施: Radiation (Radiation)
结局指标
主要结局
To assess the safe delivery of an achievable level of dose escalation in a dose escalated and intensified RT regime delivered via VMAT/IMRT and focused on the GTV by the proportion of grade ≥3 toxicities determined to be related to RT
时间窗: 4 years 3 months
次要结局
- To compare grade ≥3 toxicity 3, 6, 9, 12, 18 and 24 months, post-treatment, graded by NCI-CTCAE Version 4 (V4)(2 years post treatment)
- To assess Quality of life according to the EORTC QLQ-C30 and EORTC QLQ-LC13(8 years)
- To estimate the rate of overall survival; death from any cause is considered an event(8 years)
- To estimate the time to local failure (failure defined by RECIST V1.1 )(8 years)
- To estimate the rate of disease-free survival. All disease recurrences will be recorded. In disease-free survival, any tumour recurrence, development of distant metastases or death is considered an event.(8 years)
- To evaluate tumour response at 6, 12 and 24 months (response measured by RECIST V1.1)(2 years)
- The estimate the time to distant metastases as assessed by imaging or biopsy(8 years)
- To assess the MTD to the oesophagus. The MTD is defined as the highest dose that does not cause unacceptable toxicities. Toxicities of interest are any CTCAE V4 grade ≥3 oesophageal toxicity determined to be related to radiation therapy.(5 years)
- The change in pulmonary function post-treatment will be analysed by calculating the differences in measurements from baseline to the 1-year follow-up(1 year)