Erlotinib and Celecoxib in Treating Patients With Stage IIIB or Stage IV Recurrent Non-Small Cell Lung Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer

Treatments: Drug: erlotinib hydrochloride; Drug: celecoxib; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: NIH

Identifiers

NCT00062101

NCI-2012-02720

LUNG 2002-01

CDR0000304495

NCI-5416

Details and patient eligibility

About

This phase II trial is studying how well giving erlotinib together with celecoxib works in treating patients with recurrent stage IIIB or stage IV non-small cell lung cancer. Erlotinib and celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Celecoxib may slow the growth of a tumor by stopping blood flow to the tumor. Combining erlotinib with celecoxib may kill more tumor cells.

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Full description

PRIMARY OBJECTIVES:

I. Determine the response rate of patients with stage IIIB or IV recurrent non-small cell lung cancer treated with erlotinib and celecoxib as second-line therapy.

SECONDARY OBJECTIVES:

I. Determine the time to progression in patients treated with this regimen. II. Determine the survival duration of patients treated with this regimen. III. Determine the toxicity of this regimen in these patients. IV. Correlate the expression of epidermal growth factor receptor and cyclooxygenase-2 in tumor specimens with response, time to progression, and survival in patients treated with this regimen.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

Group 1: Patients receive oral erlotinib once daily and oral celecoxib twice daily.

Group 2: Patients receive erlotinib as in group 1.

Treatment in both groups continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 40-80 patients will be accrued for this study within 10 months.

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically or cytologically confirmed non-small cell lung cancer

  • Stage IIIB (malignant pleural effusion only) or IV

• Recurrent disease that has progressed after 1 or 2 prior chemotherapy regimens (platinum- or nonplatinum-based)

• At least 1 unidimensionally measurable lesion*

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• Must have tissue specimen available for assays

• No brain metastases

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• More than 3 months

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin normal

• AST/ALT no greater than 2.5 times upper normal limit (ULN)

• Creatinine normal

• Creatinine clearance at least 60 mL/min

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No prior abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)

• No congenital abnormality (e.g., Fuch's dystrophy)

• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)

• No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

• Able to ingest oral medication

• No requirement for IV alimentation

• No history of peptic ulcer disease

• No active gastrointestinal ulcers

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other concurrent uncontrolled illness

• No ongoing or active infection

• No significant traumatic injury within the past 21 days

• No psychiatric illness or social situation that would preclude study compliance

• No prior allergic reactions to sulfonamides, aspirin, and other nonsteroidal anti-inflammatory drugs

• No prior monoclonal antibodies to epidermal growth factor receptor (EGFR)

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• No concurrent chemotherapy

• No concurrent glucocorticoids

• More than 4 weeks since prior radiotherapy and recovered

• More than 21 days since prior major surgery

• No prior surgery affecting absorption

• No prior EGFR-specific tyrosine kinases

• No concurrent anticonvulsants

• No other concurrent investigational agents

• No concurrent antiretroviral therapy for HIV-positive patients

• No concurrent antacids

• No concurrent administration of any of the following drugs:

  • Amiodarone
  • Chloramphenicol
  • Cimetidine
  • Fluvoxamine
  • Omeprazole
  • Zafirlukast
  • Clopidogrel
  • Cotrimoxazole
  • Disulfiram
  • Fluconazole
  • Fluoxetine
  • Fluvastatin
  • Fluvoxamine
  • Isoniazid
  • Itraconazole
  • Ketoconazole
  • Leflunomide
  • Metronidazole
  • Modafinil
  • Paroxetine
  • Phenylbutazone
  • Sertraline
  • Ticlopidine
  • Valproic acid

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Group I (erlotinib hydrochloride, celecoxib)

Experimental group

Description:

Patients receive oral erlotinib once daily and oral celecoxib twice daily.

Treatment:

Drug: celecoxib

Drug: erlotinib hydrochloride

Other: laboratory biomarker analysis

Group II (erlotinib hydrochloride)

Experimental group

Description:

Patients receive erlotinib as in group 1.

Treatment:

Drug: erlotinib hydrochloride

Other: laboratory biomarker analysis