Effect of Celecoxib on Survival in Patients With Advanced Non-Small Cell Lung Cancer Receiving Chemotherapy (CYCLUS)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Cox-2-Inhibitor and Chemotherapy in Non-Small Cell Lung Cancer. A Prospective Randomized Double-Blind Study|
- Overall survival [ Time Frame: Minimum follow-up 1 yr after randomization ]
- Quality of life [ Time Frame: Week 0, 3, 6, 9, 12, 20, 28, 36, 44 ]
- Progression-free survival [ Time Frame: minimum follow-up 1 yr after randomization ]
- Toxicity [ Time Frame: Within one month after stopping study drug ]
- Cardiovascular events [ Time Frame: Within one month after stopping study drug ]
- Biological parameters (plasma VEGF, proteomics) [ Time Frame: Week 0, 6, 12, and 20 ]
|Study Start Date:||May 2006|
|Estimated Study Completion Date:||September 2010|
|Estimated Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Celecoxib
Four cycles of combination chemotherapy, usually with carboplatin + gemcitabine or carboplatin + vinorelbine, plus celecoxib 400 mg b.i.d. Treatment with celecoxib is continued after completion of chemotherapy. Maximum treatment duration is one year.
Celecoxib 400 mg twice daily, orally, starting on the same day as palliative chemotherapy. Maximum duration of treatment is one year. Treatment should be terminated earlier in case of disease progression, unacceptable toxicity, or if the patient wants to stop treatment.
Placebo Comparator: Placebo
Chemotherapy as in arm 1 plus placebo capsules, b.i.d.
One capsule twice daily, starting on the same day as palliative chemotherapy. Maximum duration of treatment is one year. Treatment should be terminated earlier in case of disease progression, unacceptable toxicity, or if the patient wants to stop treatment.
The study (CYCLUS trial, CY-cyclooxygenase-2 inhibitor, Chemotherapy, LUng cancer, Survival) is a prospective randomized double-blind multicenter trial. Patients are randomized to receive celecoxib at a dose of 400 mg b.i.d. or placebo. Primary endpoint of the trial is survival. Secondary endpoints are: quality of life, progression-free survival, toxicity, cardiovascular events, and biological parameters (plasma VEGF and proteomics).
The rationale behind the study consists of preclinical observations of antitumor effect of celecoxib in NSCLC. Inhibition of angiogenesis and proliferation as well as increased apoptosis has been demonstrated. In addition, pilot studies have shown that the combination of chemotherapy and celecoxib is feasible. No unexpected toxicity has been recorded in such trials. Furthermore, a randomized study of indomethacin, prednisolone or placebo in other types of advanced cancer, mainly gastrointestinal, showed a survival advantage for patients receiving antiinflammatory treatment.
Chemotherapy is given according to the current standard of the participating institution. In practice, patients will usually receive either carboplatin + gemcitabine or carboplatin + vinorelbine. Treatment duration with chemotherapy is 4 cycles (cycle length 3 weeks) in the absence of tumour progression or prohibitive toxicity.
Treatment with the study drug starts on the first day of cancer chemotherapy. Maximum treatment duration is one year. Treatment will be stopped earlier in case of objective tumor progression, serious toxicity that is considered to be related to the study drug or if the patient wants to stop treatment.
The size of the study is based on the hypothesis that celecoxib could prolong median survival by 8 weeks as compared to 7.5 months in the placebo group. With standard statistical requirements (type I error 5%, type II error 20%), the calculated number of patients was 760.
The study was supported by the Swedish Lung Cancer Study Group and organized as a multicenter trial, with participation of seven university hospitals and six smaller hospitals. The number of new cases of NSCLC stage IIIB-IV and performance status 0-2 in Sweden is around 1200/year. It was expected that 20% of the patients could be included in the study, which would make completion possible in three years.
The study was opened for randomization on May 31, 2006. Recruitment of patients was lower than expected. The study was closed for further randomization on May 31, 2009, as originally planned. 319 patients were included. Since maximum duration of treatment with the study drug is one year, the code will be broken after May 31, 2010. Data analysis is planned to take place in summer and autumn, 2010.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00300729
|Department of Pulmonary Medicine and Allergology, Sahlgrenska University Hospital|
|Gothenburg, Sweden, 413 45|
|Section of Pulmonary Medicine, Ryhov County Hospital|
|Jönköping, Sweden, 551 85|
|Section of Pulmonary Medicine and Allergology, County Hospital of Kalmar|
|Kalmar, Sweden, 391 85|
|Department of Pulmonary Medicine, University Hospital|
|Linköping, Sweden, 581 85|
|Department of Pulmonary Medicine and Allergy, Lund University Hospital|
|Lund, Sweden, 221 85|
|Section of Pulmonary Medicine, Malmö University Hospital|
|Malmö, Sweden, 205 02|
|Department of Medicine, Skövde Hospital/KSS|
|Skövde, Sweden, 541 85|
|Department of Medicine, Trollhättan Hospital/NÄL|
|Trollhättan, Sweden, 461 85|
|Department of Medicine, Uddevalla Hospital|
|Uddevalla, Sweden, 451 80|
|Department of Pulmonary medicine, Umeå University Hospital|
|Umeå, Sweden, 901 85|
|Department of Pulmonary Medicine and Allergology, Uppsala University Hospital|
|Uppsala, Sweden, 751 85|
|Department of Medicine, Ystad Hospital|
|Ystad, Sweden, SE-27182|
|Department of Pulmonary Medicine, Örebro University Hospital|
|Örebro, Sweden, 701 85|
|Study Chair:||Sverre Sörenson, MD, PhD||Department of Medicine, Ryhov County Hospital, Jönköping, Sweden, Department of Pulmonary Medicine, University Hospital, Linköping, Sweden, and Department of Medical and Health Sciences, Linköping University, Sweden|
|Principal Investigator:||Andrea Koch, MD||Allergy Centre, University Hospital, Linköping, Sweden, Department of Pulmonary Medicine, University Hospital, Linköping, Sweden, and Department of Medical and Health Sciences, Linköping University, Sweden|