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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00046839
• Other study ID #: RTOG-0213
• Secondary ID: CDR0000069476
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 3, 2002
• Last updated: November 14, 2015
• Start date: July 2002

Study information

• Verified date: November 2015
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• celecoxib

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Akron City Hospital at Summa Health System	Akron	Ohio
United States	Albuquerque Regional Medical Center at Lovelace Sandia Health System	Albuquerque	New Mexico
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Radiation Oncology Center	Alliance	Ohio
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	CCOP - Greenville	Greenville	South Carolina
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Fox Chase Virtua Health Cancer Program - Marlton	Mount Holly	New Jersey
United States	Cancer Center at Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin
United States	Regional Radiation Oncology Center at Rome	Rome	Georgia
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	LDS Hospital	Salt Lake City	Utah
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Dixie Regional Medical Center	St. George	Utah
United States	Park Nicollet Clinic	St. Louis Park	Minnesota
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	University of Wisconsin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin
United States	Cancer Treatment Center	Wooster	Ohio
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	North Star Lodge Cancer Center	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Gore E, Bae K, Langer C, Extermann M, Movsas B, Okunieff P, Videtic G, Choy H. Phase I/II trial of a COX-2 inhibitor with limited field radiation for intermediate prognosis patients who have locally advanced non-small-cell lung cancer: radiation therapy o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Celecoxib Combined With Radiation Therapy (RT)	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	Start of treatment to 90 days	Yes
Primary	Overall Survival	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.	From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 12 months.	No