A Randomised Phase III Trial of Highly Conformal Hypofractionated Image Guided ("Stereotactic") Radiotherapy (HypoRT) Versus Conventionally Fractionated Radiotherapy (ConRT) for Inoperable Early Stage I Non-small Cell Lung Cancer (CHISEL)
18 Years
N/A
Both
Stage 1 Non Small Cell Lung Cancer
Trial Information
A Randomised Phase III Trial of Highly Conformal Hypofractionated Image Guided ("Stereotactic") Radiotherapy (HypoRT) Versus Conventionally Fractionated Radiotherapy (ConRT) for Inoperable Early Stage I Non-small Cell Lung Cancer (CHISEL)
This is a multicentre randomised phase III trial comparing hypo-fractionated
("stereotactic') radiotherapy with conventional radiotherapy with or without chemotherapy in
patients with inoperable stage 1 peripherally located non-small cell lung cancer.
The accepted standard of care for stage 1 non-small cell lung cancer (NSCLC), that is, T1 or
T2 tumors that have not metastasised to the regional lymph nodes, is surgical resection.
However, many patients with lung cancer have significant cardiovascular and respiratory co
morbidities which render them unfit for an operation. For these patients, the standard of
care is radiotherapy - conventional fractionation (ConRT) which is administered as 20-30
fractions over a period of four to six weeks. This reduces the likelihood of long term
damage to incidentally irradiated normal tissues compared with non-fractionated treatment.
Local failure for this method, varies considerably between reports ranging from 6-70% with a
median value of 40% using a current best practice for inoperable NSCLC dose of about 60 Gy.
Concomitant chemotherapy in addition to CF improves local progression free survival by 16%
at two years compared with radiotherapy alone.
Highly conformal hypo-fractionated image guided radiotherapy is an emerging technically
complex method for precision irradiation of stage 1 NSCLC using doses with a higher
biological effect than can be achieved with standard treatment techniques. Although rates of
local control using hypo-fractionation appear greater, there are risks with serious late
toxicity. However, there is recent evidence that 54-57Gy delivered in 3 fractions can be
delivered safely with no excessive toxicity, provided the tumour has a peripheral location,
the chest wall is not included in the high dose volume and the treatment plan is highly
conformal. Although hypo-fractionation under the above conditions appears to be tolerable,
and is associated with high levels of local control, the results of a small number of phase
II trials cannot be regarded as sufficient evidence to recommend it as the standard of care
for inoperable stage I NSCLC.
This randomised phase III trial tests whether highly conformal hypo-fractionated image
guided radiotherapy for peripherally located inoperable T1 and T2a NSCLC using a dose of 54
Gy in three fractions results in superior control of disease at the primary site compared
with standard care consisting of conventionally fractionated radiotherapy with or without
concomitant chemotherapy.
Treatment summary: Investigational arm - radical radiotherapy to a total dose of 54 Gy in 3
fractions of 18 Gy each, delivered weekly on days 0, 7 and 14 with a maximum deviation of
+/- 2 days from the specified time allowed. Conventional arm - radical radiotherapy to a
total dose of 60-66 Gy in 30-33 daily 2 Gy fractions over 6 weeks, with or without
chemotherapy consisting of weekly carboplatin at an AUC of 2 and paclitaxel 45 mg/m2.
Inclusion Criteria:
- Histologically or cytologically confirmed non-small cell lung cancer diagnosed within
6 weeks prior to randomisation. The following primary cancer types are eligible:
squamous cell carcinoma, adenocarcinoma, large cell carcinoma, bronchioloalveolar
cell carcinoma, large cell neuroendocrine, and non-small cell carcinoma not otherwise
specified.
- Aged 18 years or older.
- Disease stage T1N0 or T2aN0 (UICC TNM stage, 7th Ed, 2009), based on FDG PET/CT
performed within 4 weeks prior to randomisation. T stage should be based on tumour
size alone (i.e. no atelectasis).
- An ECOG performance status score of 0 or 1.
- The tumour has a peripheral location, defined as at least 1 cm beyond the mediastinum
and 2 cm beyond the bifurcation of the lobar bronchi.
- Tumour is assessed as inoperable either i) because of unfitness for surgery as
determined by the lung multidisciplinary team including thoracic surgeons and
respiratory physicians or ii) because the patient refuses surgery.
- Female patients of childbearing potential and male patients must agree to use
adequate contraception throughout the treatment phase of the study.
- If female and of childbearing potential, a negative pregnancy test was performed
within 7 days prior to randomisation.
- Patient is expected to survive and be available for follow up for two years.
- Patient has provided written informed consent for participation in this trial prior
to any protocol-specified procedures.
- Patient undergoing chemoradiation has satisfactory haematological and biochemical
parameters as described below:
- ANC ≥ 1.5 x 109,
- Platelets ≥ 100 x 109/L, Hb ≥ 100g/L,
- Creatinine clearance ≥ 40mls/min (patients with calculated creatinine clearance
≥ 40mls/min and < 60mls/min must have this confirmed by nuclear medicine GFR
scan),
- Bilirubin < 1.5 x ULN, and
- ALT or AST < 2x ULN.
Exclusion Criteria:
- Centrally located tumours (< 1.0 cm from mediastinum or < 2.0 cm from bifurcation of
lobar bronchus).
- Tumours within 1.0 cm of the chest wall.
- Prior chemotherapy.
- Previous radiotherapy to the area to be treated.
- Women who are pregnant or lactating.
- Patient with multiple synchronous primary tumours requiring radiotherapy.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Time to Local Failure
Outcome Time Frame:
Completion of the two year follow up period for all patients.
Safety Issue:
No
Principal Investigator
David Ball, MB BS, MD, FRANZCR
Investigator Role:
Study Chair
Investigator Affiliation:
Peter MacCallum Cancer Centre, Australia
Authority:
Australia: Department of Health and Ageing Therapeutic Goods Administration
Study ID:
TROG 09.02
NCT ID:
NCT01014130
Start Date:
November 2009
Completion Date:
November 2015
Related Keywords:
- Stage 1 Non Small Cell Lung Cancer
- Non Small Cell Lung Cancer
- Hypofractionated
- Stereotactic Radiotherapy
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|
