Clinical trial NCT00278148
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer stage IIIB non-small cell lung cancer
Sponsor: Nathan Pennell, MD, PhD
Start date: 2005-10-01; Completion date: 2011-02-01
Enrollment: 32 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and 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. Giving erlotinib, paclitaxel, and carboplatin together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase I/II trial is studying the best dose of erlotinib and the side effects of erlotinib, paclitaxel, and carboplatin when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for stage III non-small cell lung cancer.

Detailed description:
OBJECTIVES:

Primary

* Assess the safety and feasibility of erlotinib hydrochloride, paclitaxel, and carboplatin in combination with accelerated hyperfractionated radiotherapy in patients with stage IIIA or IIIB non-small cell lung cancer.
* Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients.
* Assess the safety and tolerability of long-term maintenance erlotinib hydrochloride after completion of adjuvant chemoradiotherapy in these patients.

Secondary

* Evaluate the clinical and pathological response rate in these patients after neoadjuvant erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy.
* Assess the impact of erlotinib hydrochloride on disease-free survival, overall survival, locoregional control, and distant metastatic control in these patients.

OUTLINE: This is an open-label, phase I dose-escalation study of erlotinib hydrochloride followed by a non-randomized phase II study.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Phase I:

  * Neoadjuvant chemoradiotherapy: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15 in the absence of disease progression or unacceptable toxicity. Patients concurrently undergo radiotherapy twice daily on days 1-5 and 8-12. Patients with complete response, partial response, or stable disease proceed to surgery. Patients who develop a medical contraindication to surgery (i.e., medically unresectable) receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as above within 2 weeks after completion of neoadjuvant chemoradiotherapy.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Surgery: Within 4 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection and then proceed to adjuvant chemoradiotherapy.
* Adjuvant chemoradiotherapy: Within 6-8 weeks after surgery, patients receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as in neoadjuvant chemoradiotherapy.
* Maintenance therapy: All patients receive oral erlotinib hydrochloride once daily for 2 years in the absence of disease progression or unacceptable toxicity.

  * Phase II: Patients receive treatment as in phase I with erlotinib hydrochloride at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Arms: arm 1: Erlotinib, Paclitaxel, and Carboplatin with Radiation

Dose Level A: 50 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin arm 2: Erlotinib, Paclitaxel, and Carboplatin with Radiation

Dose Level B: 100 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin arm 3: Erlotinib, Paclitaxel, and Carboplatin with Radiation

Dose Level C: 150 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin
Interventions: intervention 1: carboplatin intervention 2: Erlotinib intervention 3: paclitaxel intervention 4: conventional surgery intervention 5: radiation therapy
Intervention descriptions: intervention 1: AUC2 weekly x 3 weeks intervention 2: Daily intervention 3: 50mg/m2/weekly x 3 weeks intervention 4: conventional surgery intervention 5: 150 cGy bid

Protocol documents: