Clinical trial NCT01193868
Conditions: Recurrent Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2010-09-01; Completion date: 2014-04-01
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial is studying how well RO4929097 works in treating patients with advanced non-small cell lung cancer who have recently completed treatment with front-line chemotherapy. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVES:

I. To assess clinical activity of the gamma-secretase inhibitor RO4929097 in patients with non-small cell lung cancer (NSCLC) who have recently completed front-line chemotherapy for advanced disease.

II. To assess whether percent change in tumor size 6 weeks after initiation of RO4929097 correlates with tumor expression of Notch pathway markers and stem cell markers and/or with host genotype polymorphisms for selected components of the Notch pathway.

SECONDARY OBJECTIVES:

I. To assess whether response by RECIST criteria and TTF correlate with tumor expression of Notch pathway markers and stem cell markers and/or with host genotype polymorphisms for selected components of the Notch pathway.

II. To compare tumor expression of Notch pathway and stem cell markers in this patient population with expression of these markers in tumors from our tumor bank from chemo-naive NSCLC patient.

III. To correlate expression of Notch pathway markers with expression of stem cell markers.

IV. To correlate host genotype polymorphisms for selected components of the Notch pathway and other stem cell pathways with tumor expression of Notch pathway and stem cell markers.

V. To correlate the presence of tumor EGFR activating mutations with: a) notch expression, b) stem cell marker expression, and c) response to RO4929097.

VI. To assess change in expression of Notch pathway markers and stem cell markers over the 3 days of therapy in a subset of patients and to correlate this with: a) subsequent response to therapy and TTF, b) changes of each marker over the first 3 days of therapy with changes in the other markers of interest and with changes in level of tumor cell apoptosis by TUNEL assay.

VII. For patients in whom pre chemotherapy tissue can be obtained, we will compare the post chemotherapy (pre RO4929097) expression of Notch pathway and stem cell markers to those observed in the pre chemotherapy tissue.

OUTLINE:

Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood and tumor tissue samples are collected for pharmacogenetic, pharmacodynamic, and biomarker studies by IHC, FISH, and TUNEL assay.

After completion of study therapy, patients are followed up periodically.

Arms: arm 1: Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood and tumor tissue samples are collected for pharmacogenetic, pharmacodynamic, and biomarker studies by IHC, FISH, and TUNEL assay.
Interventions: intervention 1: gamma-secretase/Notch signalling pathway inhibitor RO4929097 intervention 2: laboratory biomarker analysis intervention 3: pharmacological study
Intervention descriptions: intervention 1: Given orally intervention 2: Correlative studies intervention 3: Correlative studies

Protocol documents: