Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Cetuximab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Unresectable Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	RTOG-0324 NCT00081302

Objectives

Primary

1. Determine the feasibility of cetuximab when administered concurrently with paclitaxel, carboplatin, and radiotherapy, in terms of safety and compliance, in patients with unresectable stage IIIA or IIIB non-small cell lung cancer.

Secondary

1. Determine the response rate (complete and partial) in patients treated with this regimen.
2. Determine the overall survival (1- and 2-year survival rate and median survival) of patients treated with this regimen.
3. Determine the time to disease progression (at 1 and 2 years) in patients treated with this regimen.
4. Correlate epidermal growth factor receptor expression with the toxicity of this regimen and response, overall survival, and progression in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of 1 of the following subtypes:
  • Squamous cell carcinoma
  • Adenocarcinoma (including bronchoalveolar cell)
  • Large cell anaplastic carcinoma (including giant and clear cell carcinomas)
  • Poorly differentiated/not otherwise specified NSCLC



• Stage IIIA (T1-2, N2, M0 or T3, N1-2, M0) or IIIB (T4, any N, M0 or any T, N2-3, M0)
  • If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least 1 of the nodes must be cytologically or histologically positive



• Unresectable disease
  • No totally resected tumors



• Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiation boost field and the boost volume is limited to < 50% of the ipsilateral lung volume



• Measurable disease



• Transudate, cytologically negative, non-bloody pleural effusions allowed provided the tumor can be encompassed within a reasonable field of radiotherapy
  • Pleural effusions seen on a chest CT scan are allowed provided they are not visible on a chest x-ray and are too small to tap



• No asymptomatic or symptomatic brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• No prior drugs that target the epidermal growth factor receptor pathway
• No prior chimerized monoclonal antibody therapy
• No other concurrent immunotherapy
• No concurrent colony-stimulating factors (i.e., filgrastim [G-CSF] and sargramostim [GM-CSF])
  • Concurrent epoetin alfa allowed

Chemotherapy

• No prior systemic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes) or steroids for acute symptom management, adrenal failure, septic shock, or as antiemetics

Radiotherapy

• No prior thoracic or neck radiotherapy
• No concurrent intensity-modulated radiotherapy

Surgery

• Recovered from prior exploratory thoracotomy
• No prior surgical resection of the present cancer

Other

• More than 30 days since prior participation in another clinical trial
• No concurrent participation in another clinical trial
• No other concurrent anticancer therapy
• No amifostine during or for 3 months after study radiotherapy

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL (transfusion independent)

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• SGOT or SGPT ≤ 3 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No significant history of cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No uncompensated congestive heart failure
• No myocardial infarction within the past year
• No cardiac ventricular arrhythmias requiring medication
• LVEF normal by MUGA or echocardiogram

Pulmonary

• No history of interstitial pneumonitis
• No history of severe chronic obstructive pulmonary disease requiring 3 or more hospitalizations within the past year
• FEV₁ ≥ 1,200 cc
• No active pulmonary infection unresponsive to conventional antibiotics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study therapy
• Glucose ≤ 2 times ULN
• No more than 5% weight loss within the past 3 months
• No known allergy to murine proteins or Cremophor EL
• No neuropathy grade 2 or greater
• No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other in situ cancers

Expected Enrollment

A total of 84 patients will be accrued for this study within 1 year.

Outline

This is a multicenter study.

• Cetuximab loading dose (week 1): Patients receive a loading dose of cetuximab IV over 2 hours on day 1.



• Concurrent cetuximab and chemoradiotherapy (weeks 2-8): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50-53.



• Consolidation therapy (weeks 9-17): Patients receive cetuximab IV over 1 hour on days 57, 64, 71, 78, 85, 92, 99, 106, and 113. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 78 and 99.

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

Patients are followed at 30 days, every 3 months for 2 years, every 4 months for 2 years, and then annually thereafter.

Blumenschein GR, Paulus R, Curran WJ, et al.: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): A report of the 2 year and median survival (MS) for the RTOG 0324 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-7516, 2008.

Olsen CC, Paulus R, Komaki R, et al.: RTOG 0324: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients with stage IIIA/B non-small cell lung cancer (NSCLC)--Association between EGFR gene copy number and patients' outcome. [Abstract] J Clin Oncol 26 (Suppl 15): A-7607, 2008.

Blumenschein G Jr, Moughan J, Curran W, et al.: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (pts) with stage III A/B non-small cell lung cancer (NSCLC): an interim report of the RTOG 0324 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-7531, 392s, 2007.

Komaki R, Moughan J, Ang K, et al.: RTOG 0324: a phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): correlation between EGFR expression and the patients' outcome. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-101, S57-58, 2007.

Werner-Wasik M, Swann S, Curran W, et al.: A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): an interim overall toxicity report of the RTOG 0324 trial. [Abstract] J Clin Oncol 23 (Suppl 16): A-7135, 654s, 2005.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

George Blumenschein, MD, Protocol chair		Ph: 713-792-6363; 800-392-1611

Registry Information
Official Title		A Phase II Study Of Cetuximab (C225) In Combination With Chemoradiation In Patients With Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)
Trial Start Date		2004-03-08
Registered in ClinicalTrials.gov		NCT00081302
Date Submitted to PDQ		2004-01-06
Information Last Verified		2005-06-10
NCI Grant/Contract Number		U10-CA21661

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