Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer stage IIIB non-small cell lung cancer adenocarcinoma of the lung large cell lung cancer squamous cell lung cancer
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 24
Healthy volunteers: no

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving docetaxel and cetuximab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with cetuximab and radiation therapy in treating patients with stage III non-small cell lung cancer.

Detailed description:
OBJECTIVES:

Primary

* Test the feasibility and toxicity of combined cetuximab, weekly docetaxel, and concurrent radiotherapy in patients with poor-risk stage III non-small cell lung cancer (NSCLC).

Secondary

* Evaluate response rates (confirmed and unconfirmed, complete and partial) as well as overall and progression-free survival.
* Correlate EGFR mutations, KRAS mutations, EGFR/HER2 gene copy number detected by FISH, and protein expression by immunohistochemistry of EGFR-HER signaling pathways, phosphorylation, proliferative markers, apoptotic markers, selected oncogene markers, and markers for angiogenesis in biopsied pre-treatment tumor tissues with response and survival outcomes.
* Explore possible associations between changes in plasma angiogenic factors (VEGF, IL-8, bFGF) and cytokine levels (IL-6, IL-1α, ICAM, TGF-β, and others) and the risk of treatment-related pneumonitis and esophagitis.

OUTLINE: Patients are enrolled sequentially to 1 of 2 treatment groups.

* Cohort 1: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22.
* Cohort 2: Patients receive cetuximab as in group 1 followed by docetaxel IV over 15-30 minutes on days 8, 15, and 22 of course 1 and on days 1, 8, 15, and 22 of course 2.

Initially, 27 patients will be enrolled in Cohort 1. Once all patients in Cohort 1 have discontinued treatment, if toxicity rates are acceptable per protocol specifications, an additional 27 patients will be enrolled to Cohort 2. Treatment in both cohorts repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. All patients also undergo radiotherapy once daily, 5 days a week, beginning on day 8 of course 1 and continuing through course 2 (approximately 7 weeks). Patients with no progressive disease then receive cetuximab alone once weekly. Treatment with cetuximab alone continues in the absence of disease progression for up to 2 years.

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

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: cetuximab intervention 2: docetaxel intervention 3: radiation therapy
Intervention descriptions: intervention 1: Cohorts 1 and 2: 400 mg/m2 (initial dose) 2 hour IV infusion on Day 1, Cycle 1 only.

250 mg/m2, 1 hour IV infusion on Days 8 , 15 and 22 during Cycle 1. 250 mg/m2 (subsequent doses), 1 hour IV infusion on Days 1, 8 , 15 and 22 during subsequent cycles. intervention 2: Cohort 2 ONLY: 20 mg/m2 IV over 15 - 30 minutes on Days 8, 15 and 22 of Cycle 1. Concurrent with RT and cetuximab starting at Week 2.

20 mg/m2 IV over 15 - 30 minutes on Days 1, 8, 15 and 22 of Cycle 2. intervention 3: Radiation therapy should begin on Day 8 of Cycle 1 and continue through the end of Cycle 2. Refer to Section 12.1 for Radiation Therapy Review.

RT prescription should be PTV (GTV + 2-cm margins on CT scan) to 6,480 cGy in 36 fractions given 5 days a week, 180 cGy per day. The dose is prescribed to the isocenter. The entire treatment should be planned prior to starting treatment to ensure that the plan meets protocol specifications.

Protocol document: