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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by University Hospital, Linkoeping.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Swedish Lung Cancer Study Group
Pfizer
Information provided by:
University Hospital, Linkoeping
ClinicalTrials.gov Identifier:
NCT00300729
First received: March 8, 2006
Last updated: June 29, 2009
Last verified: June 2009
  Purpose

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).


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Celecoxib
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Linkoeping:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Minimum follow-up 1 yr after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Quality of life [ Time Frame: Week 0, 3, 6, 9, 12, 20, 28, 36, 44 ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: minimum follow-up 1 yr after randomization ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Within one month after stopping study drug ] [ Designated as safety issue: Yes ]
  • Cardiovascular events [ Time Frame: Within one month after stopping study drug ] [ Designated as safety issue: Yes ]
  • Biological parameters (plasma VEGF, proteomics) [ Time Frame: Week 0, 6, 12, and 20 ] [ Designated as safety issue: No ]

Enrollment: 319
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)
Arms Assigned Interventions
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.
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.
Other Names:
  • Celebra
  • Onsenal
Placebo Comparator: Placebo
Chemotherapy as in arm 1 plus placebo capsules, b.i.d.
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00300729

Locations
Sweden
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
Sponsors and Collaborators
University Hospital, Linkoeping
Swedish Lung Cancer Study Group
Pfizer
Investigators
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
  More Information

No publications provided by University Hospital, Linkoeping

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sverre Sörenson, MD, PhD, Swedish Lung Cancer Study Group
ClinicalTrials.gov Identifier: NCT00300729     History of Changes
Other Study ID Numbers: SLCSG0501
Study First Received: March 8, 2006
Last Updated: June 29, 2009
Health Authority: Sweden: Medical Products Agency

Keywords provided by University Hospital, Linkoeping:
Cyclooxygenase-2 inhibitors
Celecoxib
Carcinoma, non-small-cell lung
Antineoplastic agents
Therapy, palliative
Survival

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014