S0342: Paclitaxel, Carboplatin, and Cetuximab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

SWOG Cancer Research Network

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Drug: carboplatin; Drug: cetuximab; Drug: paclitaxel

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00085501

S0342 (Other Identifier)

CDR0000370806

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with a monoclonal antibody may kill more tumor cells. It is not yet known whether cetuximab is more effective when given at the same time as chemotherapy or following chemotherapy.

PURPOSE: This randomized phase II trial is studying how well giving cetuximab at the same time as combination chemotherapy works compared to giving cetuximab after combination chemotherapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Full description

OBJECTIVES:

Primary

• Compare overall survival of patients with selected stage IIIB or stage IV non-small cell lung cancer treated with concurrent vs sequential paclitaxel, carboplatin, and cetuximab.

Secondary

• Compare response rates (confirmed and unconfirmed, complete and partial) in patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Correlate epidermal growth factor receptor polymorphisms and downstream biomarkers with response to cetuximab in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I (concurrent cetuximab): Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1, 8, and 15 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 8. Treatment repeats every 21 days for a total of 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity. Beginning on week 13, patients receive single-agent cetuximab IV over 1 hour once weekly in the absence of disease progression or unacceptable toxicity.
• Arm II (sequential cetuximab): Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity. Beginning on week 13, patients receive single-agent cetuximab IV over 1 hour (over 2 hours on week 13 only) once weekly in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 180 patients (90 per treatment arm) will be accrued for this study within 9 months.

Enrollment: 242 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 (NSCLC) of one of the following stages:

  • Newly diagnosed selected stage IIIB disease (T4 lesion due to malignant pleural effusion, any N, M0)
  • Newly diagnosed stage IV disease (any T, any N, M1)
  • Recurrent stage IV disease after prior surgery or radiotherapy

• The following subtypes are eligible:

  • Adenocarcinoma
  • Squamous cell carcinoma
  • Large cell carcinoma
  • Unspecified

• Measurable disease by CT scan, MRI, x-ray, or physical exam

  • Pleural effusions, ascites, or laboratory parameters are not acceptable as the only evidence of disease
  • Not within prior radiotherapy field unless a new lesion is present
  • Not within area of prior surgical resection

• No known brain metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 mg/dL

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• SGOT or SGPT ≤ 2 times ULN
• Alkaline phosphatase ≤ 2 times ULN
• No known acute hepatitis

Renal

• Creatinine ≤ ULN
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No significant cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
• No active or uncontrolled infection
• No sensory neuropathy ≥ grade 2
• No known human anti-mouse antibodies
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy for NSCLC
• No prior chimeric or murine monoclonal antibody therapy
• No prior cetuximab

Chemotherapy

• No prior systemic chemotherapy for NSCLC

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• At least 2 weeks since prior thoracic or major surgery and recovered

Other

• No prior gefitinib or other investigational agents that target the epidermal growth factor receptor pathway

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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242 participants in 2 patient groups

1

Active Comparator group

Treatment:

Drug: cetuximab

Drug: paclitaxel

Drug: carboplatin

2

Active Comparator group

Treatment:

Drug: cetuximab

Drug: paclitaxel

Drug: carboplatin