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)

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Lead-In Ridaforolimus; Drug: Comparator: Blinded Ridaforolimus; Drug: Comparator: Blinded Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Lead-In Ridaforolimus; 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.; Other Names: MK-8669; AP23573; Deforolimus (until May, 2009); Drug: Comparator: Blinded Placebo; Four tablets of blinded placebo (to match ridaforolimus) administered daily for 5 consecutive days each week followed by 2 days of treatment holiday
Experimental: Ridaforolimus	Drug: Lead-In Ridaforolimus; 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.; Other Names: MK-8669; AP23573; Deforolimus (until May, 2009); Drug: Comparator: Blinded Ridaforolimus; Four tablets of blinded ridaforolimus administered daily for 5 consecutive days each week followed by 2 days days of treatment holiday; Other Names: MK-8669; AP23573; Deforolimus (until May, 2009)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Ariad Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: January 7, 2009
• First Submitted That Met QC Criteria: January 7, 2009
• First Posted (Estimate): January 8, 2009

Study Record Updates

• Last Update Posted (Estimate): January 21, 2015
• Last Update Submitted That Met QC Criteria: January 19, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 8669-021; 2008_599