Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGLead-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.
DRUGComparator: Blinded Ridaforolimus
Four tablets of blinded ridaforolimus administered daily for 5 consecutive days each week followed by 2 days days of treatment holiday
DRUGComparator: 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
Sponsors
Ariad Pharmaceuticals
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) in the randomized population | Randomization (Week 8) and every 8 weeks until progressive disease or death |
Secondary
| 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 |
Outcome results
None listed