A Study of Ridaforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations (MK-8669-021 AM1)

Study Overview
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Brief Summary
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This is a randomized discontinuation study of ridaforolimus in patients with advanced NSCLC who have failed at least 1 but no more than 3 prior treatment regimens and who have KRAS mutant lung cancer. Following 8 weeks of open-label ridaforolimus lead-in there will be an assessment of disease status. Patients assessed by the investigator to have stable disease after 8 weeks will be randomized to double-blind treatment with ridaforolimus or placebo. Patients assessed to have partial or complete response will continue on open-label ridaforolimus. Patients assessed to have disease progression will be discontinued from study.

Detailed Description
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Allocation and Arms Additional Information: All Patients will receive an 8-week open-label lead-in treatment of ridaforolimus. After this 8 week period patients will be re-assessed for disease status. Patients who are stable after 8 weeks are randomized in a double-blind fashion to continue treatment with ridaforolimus or to a placebo until disease progression. (Those patients who have stable disease but are randomized to placebo may cross-over to open-label ridaforolimus at the time of disease progression.) Those patients with tumor shrinkage during the open-label lead-in treatment will continue on open-label ridaforolimus, while those patients who have disease progression at 8-weeks are taken off-study.

Official Title
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A Randomized Discontinuation Phase II Trial of Ridaforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients With KRAS Mutations

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Lead-In Ridaforolimus
* Drug: Comparator: Blinded Ridaforolimus
* Drug: Comparator: Blinded Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has histologically confirmed stage IIIB/IV non-small cell lung cancer Patient has a documented mutation of the KRAS gene Patient has evidence of disease progression following 1 but no more than 3 prior chemotherapy regimens A minimum of 4 weeks has passed since the most recent anti-cancer treatment Women of childbearing potential must have a negative pregnancy test prior to start of therapy and must use an approved contraceptive method for the duration of the study Patient has adequate organ function Patient has performance status of <=2 on Eastern Cooperative Oncology Group (ECOG) performance scale Patient is >=18 years of age Exclusion Criteria: Patient has received more than 2 prior chemotherapy regimens for the treatment lung cancer Patient is known to have active brain metastases Patient is currently participating or has participated in an investigational drug study within 30 days Patient is known to be Human Immunodeficiency Virus (HIV) positive or has a known history of Hepatitis B or C Patient has an active infection requiring prescribed intervention Patient has newly diagnosed or un-controlled Type 1 or 2 diabetes

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ridaforolimus<br> | Drug: Lead-In Ridaforolimus<br>* Four 10mg tablets of ridaforolimus once daily for five consecutive days each week followed by 2 days days of treatment holiday, during the 8 week lead in treatment period.<br>* Other names: Deforolimus (until May, 2009);Drug: Comparator: Blinded Ridaforolimus<br>* Four tablets of blinded ridaforolimus administered daily for 5 consecutive days each week followed by 2 days days of treatment holiday<br>* Other names: Deforolimus (until May, 2009);|
| Placebo Comparator: Placebo<br> | Drug: Lead-In Ridaforolimus<br>* Four 10mg tablets of ridaforolimus once daily for five consecutive days each week followed by 2 days days of treatment holiday, during the 8 week lead in treatment period.<br>* Other names: Deforolimus (until May, 2009);Drug: Comparator: Blinded Placebo<br>* Four tablets of blinded placebo (to match ridaforolimus) administered daily for 5 consecutive days each week followed by 2 days of treatment holiday<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) in the randomized population |  | Randomization (Week 8) and every 8 weeks until progressive disease or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) in the full analysis population |  | Study entry (Visit 1) and every 8 weeks until progressive disease or death | 
| Overall survival (OS) in the full analysis population |  | From study entry (Visit 1) to death due to any cause | 
| OS in the randomized population |  | From study entry (Visit 1) to death due to any cause | 
| PFS in the full analysis population |  | Study entry (Visit 1) and every 8 weeks until progressive disease or death |