Celecoxib and Radiation Therapy in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00046839
First received: October 3, 2002
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Celecoxib may stop the growth of tumor cells by stopping blood flow to the tumor and may make the tumor cells more sensitive to radiation therapy.

PURPOSE: Phase I/II trial to study the effectiveness of combining celecoxib with radiation therapy in treating patients who have locally advanced non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Drug: celecoxib
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of a COX-2 Inhibitor, Celebrex (Celecoxib), [National Screening Committee# 719627] With Limited Field Radiation for Intermediate Prognosis Patients With Locally Advanced Non-Small Cell Lung Cancer, With Analysis of Prognostic Factors

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Celecoxib Combined With Radiation Therapy (RT) [ Time Frame: Start of treatment to 90 days ] [ Designated as safety issue: Yes ]

    Patients were followed for at least 90 days from start of RT and carefully evaluated with respect to treatment morbidity. A dose limiting toxicity (DLT) was defined as grade 3 or 4 nonhematologic (excluding nausea, vomiting, and alopecia) and grade 4 hematologic toxicities. Six patients were to be accrued at each dose level. If no more than three of the six patients experienced a DLT then that dose level was considered acceptable and dose escalation occurred by accruing six more patients at the next dose level. Otherwise, the preceding dose level, if any, would be declared the MTD. The MTD would be used for the Phase II arm. At a given dose, the probability of halting dose escalation when the true toxicity is 50% or higher is at least 66% (power). In addition, if the true DLT rate is instead 20%, there will still be a 10% probability of halting dose escalation at a given dose level (type I error).

    Rating scale: 0 = not the MTD, 1 = MTD


  • Overall Survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 12 months. ] [ Designated as safety issue: No ]
    Because only 21 patients (18 analyzable) out of 128 planned were accrued on this study, all analyzable patients were combined to report overall survival. The original study design planned for a comparison to a historical control, but due to the small number of patients, survival time is only reported, not tested.


Enrollment: 21
Study Start Date: July 2002
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: Celecoxib 200mg BID + RT

COX-2 Inhibitor: Celecoxib 200 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression.

Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.

Drug: celecoxib
Other Name: COX-2 Inhibitor
Radiation: radiation therapy
Experimental: Phase I: Celecoxib 400mg BID + RT

COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression.

Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.

Drug: celecoxib
Other Name: COX-2 Inhibitor
Radiation: radiation therapy
Experimental: Phase II: Celecoxib 400mg BID + RT

COX-2 Inhibitor: Celecoxib 400 mg b.i.d, 7 days/week begins 5 days prior to start of radiation therapy (RT). Once RT begins, Celecoxib a.m. dose 1-2 hours prior to RT. Administer for 2 years or until disease progression.

Concurrent Radiation Therapy: 2 Gy daily, 30-33 fractions, 5 days/week for 6-7 weeks, for a total dose of 60-66 Gy; or 3 Gy daily, 15 fractions, 5 days/week for 3-4 weeks for a total dose of 45 Gy.

Drug: celecoxib
Other Name: COX-2 Inhibitor
Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose and the recommended phase II dose of concurrent celecoxib and limited-field radiotherapy in intermediate-prognosis patients with locally advanced non-small cell lung cancer.
  • Determine the efficacy and toxicity of this regimen in these patients.
  • Determine how the predictors of mortality in the general population (i.e., comorbid conditions, functional status, quality of life, and psychological status) influence prognosis, toxicity, and outcomes of therapy in patients treated with this regimen.
  • Correlate circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8 (IL8) with survival in patients treated with this regimen.
  • Correlate circulating levels of interleukin-1 (IL1), interleukin-6 (IL6), and transforming growth factor-beta (TGFB) with pulmonary toxicity in patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of celecoxib followed by a phase II, multicenter study.

  • Phase I: Patients receive oral celecoxib twice daily. Beginning on day 6, patients undergo thoracic radiotherapy 5 days a week for 3-6.5 weeks . Patients continue to receive celecoxib for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Phase II: If fewer than 3 of the first 6 patients experience dose-limiting toxicity, then the dose of celecoxib is escalated for all patients in the study, including those in the first cohort.

Quality of life is assessed at baseline and at 3, 6, and 12 months after start of therapy.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-12 patients will be accrued for the phase I portion of this study and a total of 116 patients will be accrued for the phase II portion of this study within 25 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer

    • Inoperable stage IIB OR
    • Unresectable stage IIIA or IIIB
    • No evidence of hematogenous metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 2 AND more than 5% weight loss over the past 3 months OR
  • Zubrod 0-1 AND less than 5% weight loss over the past 3 months and refuses chemotherapy or are medically unable to tolerate combined modality therapy

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin no greater than 2 times upper limit of normal
  • International Normalized Ratio (INR) no greater than 3.0 if taking warfarin

Renal

  • Creatinine clearance at least 50 mL/min

Other

  • No active gastrointestinal ulcers or bleeding within the past 3 months
  • No other malignancy within the past 3 years except nonmelanoma skin cancer
  • No known hypersensitivity to celecoxib
  • No prior allergic-type reactions to sulfonamides
  • No prior asthma, urticaria, or allergic-type reactions to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior neoadjuvant chemotherapy
  • No concurrent chemotherapy

Endocrine therapy

  • No concurrent corticosteroids

Radiotherapy

  • No prior thoracic radiotherapy

Surgery

  • No prior complete or subtotal tumor resection

Other

  • No concurrent NSAIDs, lithium, furosemide, or angiotensin-converting enzyme inhibitors
  • Concurrent aspirin (325 mg/day) for cardioprotection allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00046839

  Show 44 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Elizabeth M. Gore, MD Medical College of Wisconsin
  More Information

Additional Information:
Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00046839     History of Changes
Other Study ID Numbers: RTOG-0213, CDR0000069476
Study First Received: October 3, 2002
Results First Received: January 28, 2014
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB 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
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
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 23, 2014