Clinical trial NCT00818675: 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)
Official title: A Randomized Discontinuation Phase II Trial of Ridaforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients With KRAS Mutations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Ariad Pharmaceuticals
First posted: 2009-01-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS) in the randomized population
timeFrame: Randomization (Week 8) and every 8 weeks until progressive disease or death
Secondary outcomes:
measure: Overall response rate (ORR) in the full analysis population
timeFrame: Study entry (Visit 1) and every 8 weeks until progressive disease or death
measure: Overall survival (OS) in the full analysis population
timeFrame: From study entry (Visit 1) to death due to any cause
measure: OS in the randomized population
timeFrame: From study entry (Visit 1) to death due to any cause
measure: PFS in the full analysis population
timeFrame: Study entry (Visit 1) and every 8 weeks until progressive disease or death
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References: