Paclitaxel and Carboplatin With or Without Celecoxib Before Surgery in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborators:
Pharmacia
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00062179
First received: June 5, 2003
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

RATIONALE: Drugs used in chemotherapy such as paclitaxel and carboplatin use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug, may stop the growth of tumor cells by stopping blood flow to the tumor, and/or may block the enzymes necessary for tumor cell growth. Giving combination chemotherapy with celecoxib before surgery may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving paclitaxel together with carboplatin followed by surgery works compared to giving paclitaxel together with carboplatin and celecoxib followed by surgery in treating patients with stage IIIA non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Drug: carboplatin
Drug: celecoxib
Drug: paclitaxel
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized Double Blind Phase II Study of Preoperative Celecoxib/Paclitaxel/Carboplatin for Stage IIIA Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Rates of complete pathological response and/or minimal residual microscopic disease at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical response at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Difference in time to progression, disease-free survival, and overall survival between Arm I and Arm II at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Toxicity in patients with paclitaxel/carboplatin/celecoxib vs. paclitaxel/carboplatin/placebo [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: March 2003
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: paclitaxel/carboplatin/celecoxib
Paclitaxel: 225 mg/m2 by 3-hour intravenous infusion Carboplatin: dosed at an AUC of 6 by the Calvert Formula Celecoxib: 400 mg po BID 3 cycles of paclitaxel and carboplatin 21 days apart celecoxib 3-7 days before first dose of chemotherapy
Drug: carboplatin
Carboplatin: dosed at an AUC of 6 by the Calvert Formula 3 cycles of carboplatin 21 days apart
Drug: celecoxib
Celecoxib: 400 mg po BID celecoxib 3-7 days before first dose of chemotherapy
Drug: paclitaxel
Paclitaxel: 225 mg/m2 by 3-hour intravenous infusion 3 cycles of paclitaxel 21 days apart
Placebo Comparator: paclitaxel/Carboplatin/Placebo
Paclitaxel: 225 mg/m2 by 3-hour intravenous infusion Carboplatin: dosed at an AUC of 6 by the Calvert Formula Placebo 3 cycles of paclitaxel and carboplatin 21 days apart Placebo 3-7 days before first dose of chemotherapy
Drug: carboplatin
Carboplatin: dosed at an AUC of 6 by the Calvert Formula 3 cycles of carboplatin 21 days apart
Drug: paclitaxel
Paclitaxel: 225 mg/m2 by 3-hour intravenous infusion 3 cycles of paclitaxel 21 days apart
Other: Placebo
placebo 3-7 days before first dose of chemotherapy

Detailed Description:

OBJECTIVES:

  • Compare the complete pathological response rate and/or minimal residual microscopic disease in patients with stage IIIA non-small cell lung cancer treated with preoperative paclitaxel and carboplatin with vs without celecoxib.
  • Compare the clinical response rate in patients treated with these regimens.
  • Compare chemotherapy-related toxicity in patients treated with these regimens.
  • Compare the time to progression, disease-free survival, and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to use of aspirin for prior cardiovascular disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on days 1, 22, and 43. Patients also receive oral celecoxib twice daily beginning on day 1 and continuing until the morning of surgical resection.
  • Arm II: Patients receive paclitaxel and carboplatin as in arm I and an oral placebo twice daily beginning on day 1 and continuing until the morning of surgical resection.

In both arms, patients undergo surgical resection and complete mediastinal lymph node dissection within 3-6 weeks after completion of chemotherapy. Patients resume oral celecoxib or placebo twice daily within 28-42 days after surgery and continue until 3 years from the date of randomization in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3-6 months.

PROJECTED ACCRUAL: A total of 110 patients (55 per treatment arm) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with biopsy proven non-small cell lung cancer clinical stage IIIA
  • Mediastinoscopy positive N2 disease is mandatory
  • The disease must be deemed potentially resectable by the thoracic surgeon
  • Karnofsky performance status > 80%
  • Pulmonary function must be acceptable for surgery according to institutional standards
  • Acceptable hepatic, renal and bone marrow function

    • Total serum bilirubin < ULN
    • AST and/or ALT < 2.5x ULN
    • Alkaline phosphatase < 2.5x ULN
    • Serum creatinine < 2.0 mg/mm3
    • White blood cell > 3000/mm3
    • Platelets > 100,000/mm3
  • Age 18 or older
  • Willingness to abstain from chronic use of NSAIDs (defined as > 7 days of continuous therapy per month OR defined as frequency of > 3 times per week) for the duration of the study. For those patients on NSAIDs prior to study entry, cessation of the drug for 72 hours prior to study entry is required
  • Patients on low-dose ASA (<325 mg daily) for prophylaxis of cardiovascular disease prior to study entry may remain on that dose of ASA during this trial
  • No anticipated chronic use of steroids. Patients may take the inhaled steroids mometasone or fluticasone if medically indicated

Exclusion Criteria:

  • Patients with known hypersensitivity or allergic reactions to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates
  • Hypersensitivity to paclitaxel
  • Significant medical or psychiatric illness that would interfere with patient compliance
  • Prior malignancy within the last 3 years with the exception of non-melanoma skin cancer
  • Receiving other investigational agents during the course of this study or are < 3 weeks from completion of other clinical trial therapy
  • Patients with a history of peptic ulcer disease, bleed disorder, irritable bowel disease, inflammatory bowel syndrome, chronic diarrhea or bowel obstruction within 5 years
  • Patients receiving enzyme-inducing anticonvulsants are ineligible. Patients who require concomitant therapy with NSAIDs or COX-2 inhibitors
  • Patients with any other serious underlying medical condition that would impair the ability of the patient to receive or comply with protocol treatment
  • Patients receiving lithium or fluconazole
  • Pregnant women or women of childbearing potential that refuse to use effective contraception during the period of chemotherapy.
  • Patients with a significant history of unstable cardiovascular disease
  • Uncontrolled diabetes mellitus or uncontrolled infection, including HIV or interstitial pneumonia or interstitial fibrosis
  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: NCT00062179

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
United States, New York
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Pharmacia
Investigators
Principal Investigator: Karen Rickard Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00062179     History of Changes
Other Study ID Numbers: CDR0000304540, P30CA016042, UCLA-0208074, NYH-CMC-0902-464, PHARMACIA-COXAON-0509-106
Study First Received: June 5, 2003
Last Updated: August 2, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Jonsson Comprehensive Cancer Center:
stage IIIA non-small cell lung cancer

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
Carboplatin
Paclitaxel
Celecoxib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014