Cetuximab in Treating Patients With Recurrent or Stage IIIB or Stage IV Lung Cancer

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Biological: cetuximab

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00103207

CDR0000409755

E1504 (Other Identifier)

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase II trial is studying how well cetuximab works in treating patients with recurrent or stage IIIB or stage IV lung cancer.

Full description

OBJECTIVES:

Primary

• Determine the objective response rate in patients with recurrent or stage IIIB or IV bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features treated with cetuximab.

Secondary

• Determine the overall survival and time to progression in patients treated with this drug.
• Determine the toxic effects of this drug in these patients.
• Correlate expression of total and phosphorylated epidermal growth factor receptor (EGFR), total and phosphorylated AKT3, and total and phosphorylated MAPKinase with response in patients treated with this drug.
• Determine whether the presence of polymorphisms or mutations in the EGFR gene influences response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours once on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

ACTUAL ACCRUAL: A total of 72 patients were accrued for this study.

Enrollment: 72 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features meeting 1 of the following stage criteria:

  • Stage IIIB disease (with pleural or pericardial effusion)
  • Stage IV disease
  • Recurrent disease

• Measurable disease

• Tumor tissue available from biopsy

• Age of 18 and over

• ECOG performance status of 0-2

• Life expectancy greater than 3 months

• White blood cell (WBC) ≥ 3,000/mm^3

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Bilirubin normal

• Aspartate aminotransferase (AST) and/or alanine aminotranferease (ALT) ≤ 2.5 times upper limit of normal

• Creatinine normal OR Creatinine clearance ≥ 60 mL/min

• No more than 1 prior chemotherapy regimen for advanced BAC

• More than 3 years since prior chemotherapy for other malignancies

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for this malignancy and recovered

• HIV-positive patients are eligible provided the following criteria are met:

  • CD4 count ≥ 100/mm^3
  • Undetectable viral load within the past 3 months
  • Receiving a stable antiretroviral regimen for ≥ 4 weeks before study entry

• Fertile patients must use effective contraception

• At least 2 weeks since prior radiotherapy and recovered

Exclusion criteria

• Untreated brain metastases

  • Patients with stable brain metastases ≥ 4 weeks after external beam radiotherapy to the brain are eligible

• Acute hepatitis

• Symptomatic congestive heart failure

• Uncontrolled hypertension

• Unstable angina pectoris

• Cardiac arrhythmia

• Pregnant or nursing

• Prior allergic reaction to chimerized or murine monoclonal antibody therapy

• Documented presence of human anti-mouse antibodies

• Ongoing or active infection

• Psychiatric illness or social situation that would preclude study compliance

• Other uncontrolled illness

• Prior cetuximab

• Concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

• Other prior known epidermal growth factor receptor inhibitors (e.g., gefitinib or erlotinib)

• Other concurrent investigational agents

• Other concurrent anticancer therapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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72 participants in 1 patient group

Cetuximab

Experimental group

Description:

Cetuximab was given as a weekly intravenous (IV) infusion (over 60 minutes) at 250 mg/m2 from week 2 onwards after an initial loading dose of 400 mg/m2 (over 120 minutes) on week 1 until disease progression or unacceptable toxicity. The infusion rate of cetuximab could not exceed 5 mL/min. Each cycle will be 28 days in length. To prevent a hypersensitivity reaction, all patients were premedicated with diphenhydramine hydrochloride 50 mg (or an equivalent antihistamine) by IV (over 30-60 minutes) prior to the first dose of cetuximab. Premedication might be administered prior to subsequent doses, but at the investigator's discretion, the dose of diphenhydramine (or a similar agent) was reduced.

Treatment:

Biological: cetuximab