Clinical trial NCT00300729: Effect of Celecoxib on Survival in Patients With Advanced Non-Small Cell Lung Cancer Receiving Chemotherapy
Official title: Cox-2-Inhibitor and Chemotherapy in Non-Small Cell Lung Cancer. A Prospective Randomized Double-Blind Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Cyclooxygenase-2 inhibitors
Celecoxib
Carcinoma, non-small-cell lung
Antineoplastic agents
Therapy, palliative
Survival
Lead sponsor: University Hospital, Linkoeping
Sponsor class: OTHER
Collaborators: name: Swedish Lung Cancer Study Group
name: Pfizer
First posted: 2006-03-09
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to investigate if daily treatment with celecoxib, an inhibitor of cyclooxygenase-2, can prolong survival in patients with advanced non-small cell lung cancer who receive anticancer chemotherapy as their primary treatment. Secondary endpoints of the study are: health-related quality of life, toxicity, cardiovascular events, progression-free survival, and biological markers (VEGF, proteomics).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
* Age at least 18 years. No upper age limit.
* Disease stage IIIB or IV.
* Performance status (WHO) 0-2
* Treatment with curative intent is not possible
* No prior chemotherapy for the present disease
* Planned treatment is palliative chemotherapy
* WBC count at least 3.0, platelet count at least 100
* Bilirubin \< 1.5 \* upper reference limit (URL), ASAT and ALAT \< 3 \* URL (\<5 in case of liver metastases)
* Calculated creatinine clearance at least 40 mg/ml
* Informed oral and written consent

Exclusion criteria:

* Regular use of NSAID (except ASA at a dose of 50-100 mg daily)
* Active duodenal ulcer, ongoing gastrointestinal bleeding or inflammatory bowel disease
* Serious heart failure or serious liver disease
* Hypersensitivity so sulfonamides
* Pregnancy
* Lactation

Primary outcomes:
measure: Overall survival
timeFrame: Minimum follow-up 1 yr after randomization
Secondary outcomes:
measure: Quality of life
timeFrame: Week 0, 3, 6, 9, 12, 20, 28, 36, 44
measure: Progression-free survival
timeFrame: minimum follow-up 1 yr after randomization
measure: Toxicity
timeFrame: Within one month after stopping study drug
measure: Cardiovascular events
timeFrame: Within one month after stopping study drug
measure: Biological parameters (plasma VEGF, proteomics)
timeFrame: Week 0, 6, 12, and 20
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of Pulmonary Medicine and Allergology, Sahlgrenska University Hospital
city: Jönköping
country: Sweden
facility: Section of Pulmonary Medicine, Ryhov County Hospital
city: Kalmar
country: Sweden
facility: Section of Pulmonary Medicine and Allergology, County Hospital of Kalmar
city: Linköping
country: Sweden
facility: Department of Pulmonary Medicine, University Hospital
city: Lund
country: Sweden
facility: Department of Pulmonary Medicine and Allergy, Lund University Hospital
city: Malmö
country: Sweden
facility: Section of Pulmonary Medicine, Malmö University Hospital
city: Skövde
country: Sweden
facility: Department of Medicine, Skövde Hospital/KSS
city: Trollhättan
country: Sweden
facility: Department of Medicine, Trollhättan Hospital/NÄL
city: Uddevalla
country: Sweden
facility: Department of Medicine, Uddevalla Hospital
city: Umeå
country: Sweden
facility: Department of Pulmonary medicine, Umeå University Hospital
city: Uppsala
country: Sweden
facility: Department of Pulmonary Medicine and Allergology, Uppsala University Hospital
city: Ystad
country: Sweden
facility: Department of Medicine, Ystad Hospital
city: Örebro
country: Sweden
facility: Department of Pulmonary Medicine, Örebro University Hospital
Study officials:
affiliation: 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
name: Sverre Sörenson, MD, PhD
role: STUDY_CHAIR
affiliation: Allergy Centre, University Hospital, Linköping, Sweden, Department of Pulmonary Medicine, University Hospital, Linköping, Sweden, and Department of Medical and Health Sciences, Linköping University, Sweden
name: Andrea Koch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koch A, Bergman B, Holmberg E, Sederholm C, Ek L, Kosieradzki J, Lamberg K, Thaning L, Ydreborg SO, Sorenson S; Swedish Lung Cancer Study Group. Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: a double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group. Eur J Cancer. 2011 Jul;47(10):1546-55. doi: 10.1016/j.ejca.2011.03.035. Epub 2011 May 10.