Clinical trial NCT01282450: Concurrent and Non-concurrent Chemo-radiotherapy or Radiotherapy Alone for Patients With Oligo-metastatic Stage IV Non-small Cell Lung Cancer (NSCLC)
Official title: Concurrent and Non-concurrent Chemo-radiotherapy or Radiotherapy Alone for Patients With Oligo-metastatic Stage IV Non-small Cell Lung Cancer (NSCLC).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage IV (Oligo-metastases)
Non-small Cell Lung Cancer
Keywords: Radiotherapy
NSCLC
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
First posted: 2011-01-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: In recent years, it has become clear, that also in non-small cell lung cancer (NSCLC), a group of patients with less than 5 distant metastases may experience long-term survival when treated radically to all macroscopic cancer sites. Thus has mostly been established for individuals with so-called solitary brain metastases and to a lesser extend in solitary adrenal gland metastases, but in other metastatic subgroups, the same may be applicable. In a prospective survey in the region of the Integral Cancercentre (IKL), we could identify on a yearly base 30 patients with NSCLC who could theoretically be amendable for radical treatment of all oligo-metastatic locations. We therefore want to perform a prospective study in which patients with less than 4 oligo-metastatic sites from a primary NSCLC will be treated radically with the aim to improve long-term survival. As many discussion points remain, even after thorough discussions with chest physicians, pulmonary surgeons and colleagues from diagnostic disciplines, we decided to go for a pragmatic approach, implying that all macroscopic disease sites should be treated radically, being defined as surgery with a R0 resection or in case of an unforeseen R1 resection, followed by radiotherapy, or radiotherapy to a biological equivalent of at least 60 Gy in 30 daily fractions. In the same patient, one metastatic site may be treated with surgery and another with radical radiotherapy. Systemic treatment was not made mandatory, because it was felt that it's role is unclear in patients with early stage local cancer and with oligo-metastatic disease.

Detailed description: Eligible patients (see below) will receive radical radiotherapy to the primary tumor and the initially involved mediastinal lymph nodes to an MLD (Mean Lung Dose) of 20 +/- 1Gy, irrespective of lung function and/or to all metastatic sites to a minimal biological equivalent of 60Gy in 30 daily fractions. This may be delivered with hypofractionated stereotactic techniques or with other more protracted fractionation regimen.

Both the primary tumor, the regional N1 lymph nodes and the oligo-metastatic site(s) may be treated with surgery, as long as an R0 resection is deemed possible. Systemic treatment is not required, but should be given according to the local extend of the tumor.

Local radiotherapy will be delivered according to the protocol of MAASTRO clinic for that anatomical site.

Other dose-constraints: spinal cord max: 54Gy, brachial plexus (Dmax): 66Gy The radiation doses will be specified according to ICRU 50. Lung density corrections will be applied, as well as all standard QA procedures. Technical requirements are the same as in standard practice at MAASTRO clinic.

Eligibility criteria: Inclusion Criteria:

* Histological or cytological proven NSCLC
* UICC stage IV, or solitary metastases (\< 5), which are amendable for radical local treatment
* Performance status 0-2
* Other malignancy is allowed if controlled at the point of diagnosis

Exclusion Criteria:

* Not NSCLC or mixed NSCLC and other histologies (e.g. small cell carcinoma)
* Stage I-III, except for T4 because of pleural metastases
* Performance status 3 or more

Primary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 3 years
Secondary outcomes:
measure: Progression free survival
timeFrame: 2 years
measure: Dyspnea (CTC4.0)
timeFrame: 2 years
measure: Dysphagia (CTC 4.0)
timeFrame: 2 years
measure: Patterns of recurrence
timeFrame: 2 years
measure: Progression free survival
timeFrame: 3 years
measure: Dyspnea (CTC4.0)
timeFrame: 3 years
measure: Dysphagia (CTC4.0)
timeFrame: 3 years
measure: Patterns of recurrence
timeFrame: 3 years
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: MAASTRO clinic
state: Limburg
Study officials:
affiliation: MAASTRO clinic, Maastricht Radiation Oncology
name: Dirk De Ruysscher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: De Ruysscher D, Wanders R, van Baardwijk A, Dingemans AM, Reymen B, Houben R, Bootsma G, Pitz C, van Eijsden L, Geraedts W, Baumert BG, Lambin P. Radical treatment of non-small-cell lung cancer patients with synchronous oligometastases: long-term results of a prospective phase II trial (Nct01282450). J Thorac Oncol. 2012 Oct;7(10):1547-55. doi: 10.1097/JTO.0b013e318262caf6.