MEK Inhibitor PD-325901 To Treat Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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MEK is a critical member of the MAPK pathway involved in growth and survival of cancer cells. PD-325901 is a new drug designed to block this pathway and kill cancer cells. The purpose of this study is to study the effectiveness of PD-325901 in patients with non-small cell lung cancer. PD-325901 will be given by mouth as a pill twice a day, CT scans will be done and biopsies of a tumor and a blood sample will be taken before treatment to examine the how genes affect tumor response to the study medication. Blood samples will be taken to measure the amount of drug in the blood.

Detailed Description
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This study was terminated prematurely on 23 March 2007 due to safety issues (ocular and neurological toxicity observed in another PD-0325901 study, A4581001) as well as lack of objective responses

Official Title
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Phase 2 Study Of The MEK Inhibitor PD-0325901 In Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: PD-0325901


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented non-small cell lung cancer with metastases (Stage IV or recurrent disease) or locally advanced (Stage IIIB) with malignant pleural effusion with no expectation of further effects of prior anticancer therapy, and resolution of all acute toxic effects Adequate renal, liver, and bone marrow function, determined within 2 weeks prior to the first treatment and an ECOG status of <=1. Must have evidence of progression of disease within 6 months of most recent prior systemic anticancer therapy. Exclusion Criteria: No parathyroid disorder or history of malignancy associated hypercalcemia No ongoing radiation therapy or radio-cytotoxic therapy within prior 4 weeks; No immunotherapy, biologic therapy, hormonal, or molecular targeted therapy within prior 2 weeks No concurrent serious infection or life-threatening illness (unrelated to tumor) No history of a malignancy (other tha non-small cell lung cancer) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years. No active seizure disorders or untreated brain metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD0325901<br>15 mg BID | Drug: PD-0325901<br>* 15 mg BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the activity of PD-0325901 in advanced non-small cell lung cancer |  | Duration of trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the progression-free survival |  | Duration of trial | 
| To determine the duration of response |  | Duration of trial | 
| To determine the overall survival |  | Duration of trial | 
| To determine the safety profile of PD-0325901 |  | Duration of trial | 
| To explore pharmacogenomic and cancer biomarkers (gene and/or protein expression profiling) relationships with cancer- and treatment-related outcomes duration of response |  | Duration of trial | 
| To evaluate PD-0325901 population pharmacokinetics and explore its correlation with efficacy and safety parameters |  | Duration of trial | 
| To explore pharmacogenomic and cancer biomarkers (gene and/or protein expression profiling) relationships with cancer- and treatment-related outcomes |  | Duration of trial |