|- candidate number||4350|
|- NTR Number||NTR1527|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||7-nov-2008|
|- Secondary IDs||2008-266 VU METC|
|- Public Title||Randomized trial on chest irradiation in extensive disease small cell lung cancer.|
|- Scientific Title||Randomized trial on chest irradiation in extensive disease small cell lung cancer.|
|- hypothesis||The objective of this study is to investigate whether thoracic radiotherapy can improve 1year survival in patients with extensive disease SCLC, following a response to chemotherapy, from 27% to 37%, as measured from time of randomisation after chemotherapy|
|- Healt Condition(s) or Problem(s) studied||Radiotherapy, Small cell lung cancer (SCLC), Metastasis|
|- Inclusion criteria||1. Cytologically or histologically proven small cell lung cancer.|
2. Documented extensive disease before the start of chemotherapy.
3. Any response after 4 to 6 cycles of initial chemotherapy.
4. Chemotherapy completed.
5. Maximum delay of 4 weeks between last chemotherapy administration and randomization.
6. No evidence of brain metastases or leptomeningeal metastases.
7. No evidence of pleural metastases or pleuritis carcinomatosa.
8. No prior radiotherapy to the brain.
9. No prior radiotherapy to the thorax.
10. Age 18 years or older.
11. WHO Performance status 0 to 2.
12. Patient must be willing to receive chest irradiation.
13. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
14. Volume should be encompassable in acceptable radiation fields.
|- Exclusion criteria||None|
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2009|
|- planned closingdate||24-dec-2012|
|- Target number of participants||483|
|- Interventions||Patients with a response to chemotherapy, will receive prophylactic cranial irradiation 20 Gy in 5 fractions or 30 Gy in 10 fractions 4-5 times per week. And they will be randomized to receive either thoracic irradiation or no further therpy. For thoracic radiotherapy, 30 Gy will be delivered in 10 fractions, 4-5 times per week.|
|- Primary outcome||The primary endpoint of this trial is to achieve an increase in 1 year survival of 10% (from 27% to 37%; HR=0.76). |
The Kaplan-Meier method will be used to estimate survival at different time points, and the logrank two sided test will be used to compare therapeutic arms according to the intent to treat policy.
|- Secondary outcome||The secondary endpoints are local control, pattern of failure and toxicity. Local control is defined as the absence of disease progression in the treated lobe/lung. |
|- Timepoints||PCI and thoracic radiotherapy will commence within six weeks after the completion of chemotherapy. |
However, PCI and thoracic radiotherapy can only start at least 2 weeks after the last administration of chemotherapy, when the acute Grade 2 or higher toxicity of chemotherapy has resolved.
Acute toxicity will be recorded during treatment, and reported on the acute toxicity checklist and at end of treatment, according to CTCAE v 3.0.
Patients will be followed up at 6 weeks and at 3, 6, 9 and 12 months after randomisation in both arms, and, subsequently every 6 months until death.
This follow-up schedule must adhere to all patients, in both treatment arms.
The following examinations will be performed at each follow-up:
- Medical history and physical evaluation
- Chest X-ray
|- Trial web site||http://www.iknl.nl|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. B.J. Slotman|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. B.J. Slotman|
|- Sponsor/Initiator ||VU University Medical Center, Department of Radiation Oncology|
(Source(s) of Monetary or Material Support)
|VU University Medical Center, Department of Radiation Oncology|
|- Publications||Use of thoracic radiotherapy for extensive stage small-cell
lung cancer: a phase 3 randomised controlled trial , Slotman et al. The Lancet September 14, 2014 |
Comments in http://dx.doi.org/10.1016/
|- Brief summary||Intrathoracic tumor control is a major problem in ED-SCLC. Over 75% of patients have persisting intra-thoracic disease after initial chemotherapy, and about 90% manifest intra-thoracic disease progression at 1 year after completing initial chemotherapy [Slotman,2007].
In a trial reported by Jeremic et al., patients with ED-SCLC who had a complete response at sites of distant disease, were randomized to thoracic radiotherapy (54 Gy in 18 days) in combination with low dose chemotherapy or an additional four cycles of cisplatin/etoposide chemotherapy only [Jeremic 1999]. A total of 109 patients were randomized after induction chemotherapy, and the reported median (17 versus 11 months) and 5-year survivals (9.1% v 3.7 %,) was far higher than has been reported by any other group for ED-SCLC. This study has not yet been repeated.
In the absence of promising systemic agents that can improve local response, a logical step would be to evaluate the role of thoracic irradiation in patients with ED-SCLC who respond to chemotherapy.
|- Main changes (audit trail)||7-okt-2014: Amendment approved in February 2012. Trial was closed in december 2012. First publication in 2014. |
- Item 3: addition of "chemotherapy regimen and response evaluation according to the standard institution policy, provided that none of the existing lesions progressed"
- Item 4: change into "Chemotherapy (preferably platinum-etoposide; other regimens need approval of study-coordinator) completed. A patient can be randomized prior to the end of chemotherapy if the date of last chemotherapy is known and not more than 2 weeks in the future, and if the response criteria are met on the date of randomization. Study treatment should start within 6 weeks after last date of chemotherapy"
- Item 5: Change maximum delay into 6 weeks
- Item 6: Addition of "A contrast enhanced CT MRI scan of the brain is mandatory in case of clinical suspicion of brain metastases"
Amendement approved 2012
- Cytologically or histologically proven small cell lung cancer
-Documented extensive disease (see appendix D) before the start of chemotherapy
-Any response after 4 to 6 cycles of initial chemotherapy (chemotherapy regimen and response evaluation according to the standard institution policy, provided that none of
the existing lesions progressed)
-Chemotherapy (preferably platinum-etoposide; other regimens need approval of
study-coordinator) completed. A patient can be randomized prior to the end of
chemotherapy if the date of last chemotherapy is known and not more than 2 weeks
in the future, and if the response criteria are met on the date of randomization. Study
treatment should start within 6 weeks after last date of chemotherapy.
- Maximum interval of 6 weeks between last chemotherapy administration and
-No evidence of brain metastases or leptomeningeal metastases (A contrast
enhanced CT MRI scan of the brain is mandatory in case of clinical suspicion of brain
-No evidence of pleural metastases or pleuritis carcinomatosa
-No prior radiotherapy to the brain
-No prior radiotherapy to the thorax
- Age 18 years or older
-Performance status 0 to 2 (WHO scale, see Appendix B)
-Patient must be willing to receive chest irradiation
-Before patient registration/randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations
-Volume should be encompassable in acceptable radiation fields
|- RECORD||7-nov-2008 - 27-feb-2015|