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

NCT ID: NCT00300729

Last Updated: 2009-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

319 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-05-31

Study Completion Date

2010-09-30

Brief Summary

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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

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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.

Conditions

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Non-Small Cell Lung Cancer

Keywords

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Cyclooxygenase-2 inhibitors Celecoxib Carcinoma, non-small-cell lung Antineoplastic agents Therapy, palliative Survival

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Celecoxib

Intervention Type DRUG

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

Chemotherapy as in arm 1 plus placebo capsules, b.i.d.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Celebra Onsenal

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Swedish Lung Cancer Study Group

NETWORK

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

University Hospital, Linkoeping

OTHER

Sponsor Role lead

Responsible Party

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Swedish Lung Cancer Study Group

Principal Investigators

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Sverre Sörenson, MD, PhD

Role: STUDY_CHAIR

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

Andrea Koch, MD

Role: PRINCIPAL_INVESTIGATOR

Allergy Centre, University Hospital, Linköping, Sweden, Department of Pulmonary Medicine, University Hospital, Linköping, Sweden, and Department of Medical and Health Sciences, Linköping University, Sweden

Locations

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Department of Pulmonary Medicine and Allergology, Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Section of Pulmonary Medicine, Ryhov County Hospital

Jönköping, , Sweden

Site Status

Section of Pulmonary Medicine and Allergology, County Hospital of Kalmar

Kalmar, , Sweden

Site Status

Department of Pulmonary Medicine, University Hospital

Linköping, , Sweden

Site Status

Department of Pulmonary Medicine and Allergy, Lund University Hospital

Lund, , Sweden

Site Status

Section of Pulmonary Medicine, Malmö University Hospital

Malmo, , Sweden

Site Status

Department of Pulmonary Medicine, Örebro University Hospital

Örebro, , Sweden

Site Status

Department of Medicine, Skövde Hospital/KSS

Skövde, , Sweden

Site Status

Department of Medicine, Trollhättan Hospital/NÄL

Trollhättan, , Sweden

Site Status

Department of Medicine, Uddevalla Hospital

Uddevalla, , Sweden

Site Status

Department of Pulmonary medicine, Umeå University Hospital

Umeå, , Sweden

Site Status

Department of Pulmonary Medicine and Allergology, Uppsala University Hospital

Uppsala, , Sweden

Site Status

Department of Medicine, Ystad Hospital

Ystad, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type DERIVED
PMID: 21565487 (View on PubMed)

Other Identifiers

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SLCSG0501

Identifier Type: -

Identifier Source: org_study_id