NCT01912625

Trametinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

A Phase 1 Study of Trametinib in Combination With Chemoradiation for KRAS Mutant Non-small Cell Lung Cancer

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of trametinib when given together with combination chemotherapy and radiation therapy in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells. Giving trametinib, combination chemotherapy, and radiation therapy may be a better treatment for non-small cell lung cancer.

Detailed description

PRIMARY OBJECTIVES: I. Determine the maximum-tolerated dose (MTD) of GSK1120212 (trametinib) combined with standard chemoradiation in unresectable non-small cell lung cancer (NSCLC) and safety as measured by the rate of grade 3 or worse non-hematological toxicities occurring prior to the beginning of consolidation therapy (including all toxicities attributed to chemoradiation occurring within 10 weeks of the start of radiation therapy). II. Pharmacokinetic (PK) analysis of carboplatin, paclitaxel, and trametinib. SECONDARY OBJECTIVES: I. Response rate based on computed tomography (CT) or fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/CT imaging response assessment after completion of chemoradiation. II. Biomarker correlate to response and resistance. III. Overall survival. IV. Patterns of recurrence. V. Determine dose delay and the percentage of dose delivered for each agent. OUTLINE: This is a dose-escalation study of trametinib. CONCURRENT CHEMOTHERAPY: Patients undergo intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) once daily (QD) 5 days a week for 6 weeks. Patients receive trametinib orally (PO) QD and carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 1 hour once weekly. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients without disease progression after completion of chemoradiation proceed to consolidation chemotherapy. CONSOLIDATION CHEMOTHERAPY: Beginning 3 weeks after completion of concurrent chemoradiation, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 1 and 22. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years.

Conditions

• Recurrent Lung Non-Small Cell Carcinoma
• Stage III Lung Non-Small Cell Cancer AJCC v7
• Stage IIIA Lung Non-Small Cell Cancer AJCC v7
• Stage IIIB Lung Non-Small Cell Cancer AJCC v7

Interventions

Type	Name	Description
RADIATION	3-Dimensional Conformal Radiation Therapy	Undergo 3D-CRT
DRUG	Carboplatin	Given IV
RADIATION	Image Guided Radiation Therapy	Undergo IGRT
RADIATION	Intensity-Modulated Radiation Therapy	Undergo IMRT
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Paclitaxel	Given IV
OTHER	Pharmacological Study	Correlative studies
DRUG	Trametinib	Given PO

Timeline

• Start date: 2013-10-28
• Primary completion: 2017-11-03
• Completion: 2023-02-24
• First posted: 2013-07-31
• Last updated: 2023-05-06

Locations

5 sites across 1 country: United States