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

Radiation Therapy Oncology Group

Status and phase

Completed

Phase 2

Phase 1

Conditions

Lung Cancer

Treatments

Radiation: radiation therapy

Drug: celecoxib

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00046839

CDR0000069476

RTOG-0213

Details and patient eligibility

About

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.

Full 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.

Enrollment

21 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

21 participants in 3 patient groups

Phase I: Celecoxib 200mg BID + RT

Experimental group

Description:

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.

Treatment:

Drug: celecoxib

Radiation: radiation therapy

Phase I: Celecoxib 400mg BID + RT

Experimental group

Description:

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.

Treatment:

Drug: celecoxib

Radiation: radiation therapy

Phase II: Celecoxib 400mg BID + RT

Experimental group

Description:

Treatment:

Drug: celecoxib

Radiation: radiation therapy