Clinical trial NCT00181545: Safety Study of Individualised Radiation Dose Determination for Lung Cancer Patients.
Official title: Individualised Radiation Dose Determination on Basis of Normal Tissue Dose Constraints in Patients With Non-Small-Cell Lung Cancer: A Phase I Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small-Cell Lung Carcinoma
Keywords: Non-small cell lung carcinoma
radiotherapy
mean lung dose
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Radiotherapy is treatment of choice for inoperable lung cancer. Research has shown that the local control rate is low and the radiation often causes pneumonitis and/or esophagitis.

To predict to lung damage the mean lung dose can be calculated. This allows us to give a higher total dose to the tumor and to improve the local control rate.

Study hypothesis: It will be safe to administer a radiation dose as high as possible to the tumor, taking into account the mean lung dose, calculated by the treatment planning system.

Detailed description: Radiotherapy is treatment of choice for inoperable lung cancer. Research has shown that the survival rate as well as the local control rate is low. If chemotherapy treatment is added it leads to a slightly better outcome. The radiotherapy treatment often causes pneumonitis and/or esophagitis. So damage to the normal tissue restricts the radiation dose that can be administered.

However, several studies have shown that higher doses lead to better local control. Furthermore it is evident that the radiotherapy treatment should be given in a short time, preferably the treatment time should not exceed 32 days.

To avoid a higher toxicity the normal tissue has to be spared, but to increase the local control rate the tumor dose must be as high as possible. This dilemma can only be solved by using very sophisticated treatment planning techniques in combination with a biologically superior treatment schedule. This schedule consists of delivering radiation dose twice a day instead of once, thus keeping the overall treatment time as low as possible.

For the whole patient population, the mean lung dose can to a great extend predict the probability for developing radiation pneumonitis and the post-radiotherapy lung function. A logical next step is to determine the dose of radiotherapy on an individualised calculation of the maximum tolerated dose, being defined as the mean lung dose and the spinal cord dose.

The objective of this trial is to investigate whether individualised radiation dose calculation based on a mean lung dose and the constraints of the spinal cord, in combination with an overall treatment time of less than 32 days, and only irradiating the primary tumor and the PET scan positive mediastinal areas is safe.

Eligibility criteria: Inclusion Criteria:

* Histologically proven non-small cell lung cancer
* UICC stage I-III
* WHO performance status 0-2
* Less than 10 % weight loss the last 6 months
* In case of previous chemotherapy, radiotherapy can start after a minimum of 21 days after the last chemotherapy course
* Reasonable lung function: FEV1 ³ 60 % of the predicted value
* No recent ( \< 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction)
* No active peptic oesophagitis
* Life expectancy more than 6 months
* Measurable cancer
* Willing and able to comply with the study prescriptions
* 18 years or older
* Not pregnant and willing to take adequate contraceptive measures during the study
* Have given written informed consent before patient registration
* No previous radiotherapy to the chest

Exclusion Criteria:

* Not non-small cell histology, e.g. mesothelioma, lymphoma
* Mixed pathology, e.g. non-small cell plus small cell cancer
* Malignant pleural or pericardial effusion
* Concurrent chemotherapy with radiation
* History of prior chest radiotherapy
* Recent ( \< 3 months) myocardial infarction
* Uncontrolled infectious disease
* Distant metastases (stage IV)
* Patients with active peptic oesophagitis in the last year.
* Less than 18 years old
* Pregnant or not willing to take adequate contraceptive measures during the study

Primary outcomes:
measure: incidence of steroid dependent (grade 2 or more) radiation pneumonitis 6 months after the last radiotherapy dose.
Secondary outcomes:
measure: incidence of radiation pneumonitis according to the location of the primary tumour
measure: acute esophagitis
measure: FEV1 6 months after radiotherapy
measure: DLCO 6 months after radiotherapy
measure: late esophagitis, 6 months after radiotherapy
measure: tumor response, 70 days post chest radiotherapy
measure: quality of life
Other outcomes:
Locations:
city: Heerlen
country: Netherlands
facility: Maastircht Radiation Oncology
state: Limburg
Study officials:
affiliation: Maastricht Radiation Oncology (MAASTRO clinic)
name: Dirk De Ruysscher, PHD
role: PRINCIPAL_INVESTIGATOR
References: