Effect of Celecoxib on Survival in Patients With Advanced Non-Small Cell Lung Cancer Receiving Chemotherapy

Non-Small Cell Lung Cancer Clinical Trial

— CYCLUS  

Official title:

Cox-2-Inhibitor and Chemotherapy in Non-Small Cell Lung Cancer. A Prospective Randomized Double-Blind Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00300729
• Other study ID #: SLCSG0501
• Status: Active, not recruiting
• Phase: Phase 3
• First received: March 8, 2006
• Last updated: June 29, 2009
• Start date: May 2006
• Est. completion date: September 2010

Study information

• Verified date: June 2009
• Source: University Hospital, Linkoeping
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 319
• Est. completion date: September 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Celecoxib
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
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.

Locations

Country	Name	City	State
Sweden	Department of Pulmonary Medicine and Allergology, Sahlgrenska University Hospital	Gothenburg
Sweden	Section of Pulmonary Medicine, Ryhov County Hospital	Jönköping
Sweden	Section of Pulmonary Medicine and Allergology, County Hospital of Kalmar	Kalmar
Sweden	Department of Pulmonary Medicine, University Hospital	Linköping
Sweden	Department of Pulmonary Medicine and Allergy, Lund University Hospital	Lund
Sweden	Section of Pulmonary Medicine, Malmö University Hospital	Malmö
Sweden	Department of Pulmonary Medicine, Örebro University Hospital	Örebro
Sweden	Department of Medicine, Skövde Hospital/KSS	Skövde
Sweden	Department of Medicine, Trollhättan Hospital/NÄL	Trollhättan
Sweden	Department of Medicine, Uddevalla Hospital	Uddevalla
Sweden	Department of Pulmonary medicine, Umeå University Hospital	Umeå
Sweden	Department of Pulmonary Medicine and Allergology, Uppsala University Hospital	Uppsala
Sweden	Department of Medicine, Ystad Hospital	Ystad

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Linkoeping	Pfizer, Swedish Lung Cancer Study Group

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		Minimum follow-up 1 yr after randomization	No
Secondary	Quality of life		Week 0, 3, 6, 9, 12, 20, 28, 36, 44	No
Secondary	Progression-free survival		minimum follow-up 1 yr after randomization	No
Secondary	Toxicity		Within one month after stopping study drug	Yes
Secondary	Cardiovascular events		Within one month after stopping study drug	Yes
Secondary	Biological parameters (plasma VEGF, proteomics)		Week 0, 6, 12, and 20	No