Clinical trial NCT01836692: Isotoxic Intensity Modulated Radiotherapy (IMRT) in Stage III Non Small Cell Lung Cancer (NSCLC) - A Feasibility Study
Official title: Isotoxic Intensity Modulated Radiotherapy (IMRT) in Stage III Non Small Cell Lung Cancer (NSCLC) - A Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non Small Cell Lung Cancer
Lead sponsor: The Christie NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: British Lung Foundation
name: Sheffield Teaching Hospitals NHS Foundation Trust
name: Belfast Health and Social Care Trust
name: The Leeds Teaching Hospitals NHS Trust
name: Cambridge University Hospitals NHS Foundation Trust
name: Royal Marsden NHS Foundation Trust
name: East and North Hertfordshire NHS Trust
First posted: 2013-04-22
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is for patients having a course of chest radiotherapy treatment after receiving chemotherapy for the treatment of non-small cell lung cancer. Patients with non-small cell lung cancer have a risk of the tumour in the lung recurring or progressing after treatment.

In this study, we will investigate:

* whether giving a more targeted and individualised type of chest irradiation or radiotherapy to the lung tumour (known as Isotoxic IMRT), is practical and whether it causes side effects which can be tolerated
* whether this new method of delivering the radiotherapy can reduce the risk of the tumour in the lung recurring or progressing
* whether survival can be improved by using this new radiotherapy method

The dose of chest irradiation will be calculated specifically to suit patient's body shape, the position of the lung cancer, and how close healthy tissues are to the tumour. Radiotherapy will be delivered twice a day over a maximum period of 4.5 weeks. The duration of treatment will vary individually according to the delivered dose to the tumour area.

Detailed description: Background:

Approximately 12,000 patients are diagnosed with stage III NSCLC in the UK each year and their survival is \~15% at 5 years. As the majority of patients are not suitable for the gold standard treatment (concurrent chemo-radiotherapy (CTRT), novel strategies integrating radiotherapy (RT) technological advances and radiobiological knowledge need to be evaluated in patients treated with the alternative treatment option, sequential CTRT. There is solid evidence that improving local control in lung cancer leads to increased survival. Strategies to improve local control in stage III NSCLC include dose escalation and individualisation which are limited by the dose delivered to surrounding normal tissues. We hypothesise that this will be facilitated by the use of IMRT.

Objectives:

To demonstrate the feasibility of delivering isotoxic RT using IMRT and hyperfractionated accelerated RT in stage III NSCLC patients who are not suitable for concurrent CTRT.

Endpoints:

Primary endpoint: Delivery of isotoxic IMRT to dose \>60 Gy EQD2 (total biologically equivalent in 2 Gy fraction).

Secondary endpoints: Estimation of the suitability for lung isotoxic IMRT, estimation of proportion of patients with acute grade 3+ non haematological toxicity, estimation of late toxicity, estimation of local control/overall survival and development of a robust Quality Assurance (QA) process for lung IMRT.

Design:

Prospective multicentre, non-randomised feasibility study with early stopping rules.

35 patients will be recruited in this prospective multicentre feasibility study. Stopping rules are in place to ensure the safety of patients. We estimate that this regimen would be of added value to a national randomised phase II trial if 80% of the patients can be planned to a dose \>60 Gy EQD2.

Intervention:

Patients with stage III NSCLC, PS 0-2, not suitable for concurrent CTRT, will be treated with individualised doses of radiation based on pre-specified normal tissue doses (spinal cord, brachial plexus, lung tissue, heart and great vessels/proximal bronchial tree). Radiotherapy will be delivered twice-daily over a maximum period of 4.5 weeks using IMRT and the dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed NSCLC
* Inoperable Stage III disease (T3N1-3, any T4, any N2 -3) confirmed by PET scanning, mediastinoscopy or thoracoscopy
* Patients treated with at least 2 cycles of platinum based induction chemotherapy and able to start radiotherapy within 5 weeks of the last cycle of chemotherapy
* Tumour judged inoperable by a lung MDT
* Age 18+, no upper age limit
* Performance status (PS) - ECOG 0-2. Patients with PS 2 whose general condition is explained by disease can be included at the discretion of the local investigator. Patients with PS 2 as a result of co-morbid conditions will be excluded
* Patient considered suitable for radical RT
* Tumour that can be encompassed within a radical RT treatment volume (MLD expected to be \<20Gy)

Exclusion Criteria:

* Patients suitable for standard concurrent CTRT
* Patients only suitable for radical RT due to PS and co-morbidities

Primary outcomes:
measure: The number of participants treated with isotoxic RT (to dose >60 Gy EQD2) using IMRT & hyperfractionated accelerated RT.
timeFrame: Stage 1 (12 months) - after 19 patients have been treated with isotoxic IMRT
Secondary outcomes:
measure: The number of participants from the study population who are suitable to receive isotoxic IMRT treatment.
timeFrame: 12 months
measure: The number of participants treated with isotoxic IMRT who experience grade 3+ pulmonary toxicity
timeFrame: 12 months
measure: The number of participants treated with isotoxic IMRT who experience acute grade 3+ non haematological toxicity & other late toxicities
timeFrame: 12 months
measure: Number of participants whose disease is controlled locally & overall survival rates
timeFrame: Follow up visits every 4 months for 2 years & then 6 monthly for up to 5 years
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Belfast Health & Social Care NHS Trust - Northern Ireland Cancer Centre
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust - St James's University Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: The Christie NHS Foundation Trust
name: Corinne Faivre-Finn, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: