Clinical trial NCT00117962
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer stage IIIB non-small cell lung cancer squamous cell lung cancer large cell lung cancer adenocarcinoma of the lung bronchoalveolar cell lung cancer
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2005-09-01; Completion date: 2012-09-01
Enrollment: 109 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Cetuximab may also make tumor cells more sensitive to radiation therapy. Giving pemetrexed disodium, carboplatin, and radiation therapy together with cetuximab may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium and carboplatin together with radiation therapy with or without cetuximab works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.

Detailed description:
OBJECTIVES:

Primary

* Determine the overall survival of patients with unresectable stage III non-small cell lung cancer treated with pemetrexed disodium, carboplatin, and thoracic radiotherapy with or without cetuximab.

Secondary

* Determine the failure-free survival and response rates in patients treated with these regimens.
* Correlate epidermal growth factor receptor, erbB2, and K-ras mutations with survival and tumor response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

* Chemoradiotherapy (courses 1-4): Patients are randomized to 1 of 2 treatment arms.

  * Arm I: Patients receive pemetrexed disodium IV over 10 minutes followed by carboplatin IV over 30 minutes on days 1, 22, 43, and 64. Patients also undergo thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
  * Arm II: Patients receive pemetrexed disodium, carboplatin, and thoracic radiotherapy as in arm I. Patients also receive cetuximab IV over 2 hours on day 1 and then IV over 1 hour on days 8, 15, 22, 29, 36, and 43.
* Consolidation chemotherapy (courses 5-8): Beginning 3-5 weeks after completion of chemoradiotherapy, all patients receive consolidation chemotherapy comprising pemetrexed disodium alone IV over 10 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 10-13 months.

Arms: arm 1: Patients receive pemetrexed disodium IV over 10 minutes followed by carboplatin IV over 30 minutes on days 1, 22, 43, and 64. Patients also undergo thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. arm 2: Patients receive pemetrexed disodium, carboplatin, and thoracic radiotherapy as in arm I. Patients also receive cetuximab IV over 2 hours on day 1 and then IV over 1 hour on days 8, 15, 22, 29, 36, and 43.
Interventions: intervention 1: cetuximab intervention 2: carboplatin intervention 3: pemetrexed disodium intervention 4: radiation therapy
Intervention descriptions: intervention 1: 400 mg/sq m IV over 120 min: Day 1; Week 1 250 mg/sq m IV over 60 min weekly for 6 more weeks. intervention 2: AUC = 5 q 21 days for 4 cycles intervention 3: 500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases intervention 4: Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.

Protocol documents: