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)

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00818675
• Other study ID #: 8669-021
• Secondary ID: 2008_599
• Status: Terminated
• Phase: Phase 2
• First received: January 7, 2009
• Last updated: January 19, 2015
• Start date: March 2009
• Est. completion date: August 2012

Study information

• Verified date: January 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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.
• Comparator: Blinded Ridaforolimus
Four tablets of blinded ridaforolimus administered daily for 5 consecutive days each week followed by 2 days days of treatment holiday
• 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Ariad Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) in the randomized population		Randomization (Week 8) and every 8 weeks until progressive disease or death	No
Secondary	Overall response rate (ORR) in the full analysis population		Study entry (Visit 1) and every 8 weeks until progressive disease or death	No
Secondary	Overall survival (OS) in the full analysis population		From study entry (Visit 1) to death due to any cause	No
Secondary	OS in the randomized population		From study entry (Visit 1) to death due to any cause	No
Secondary	PFS in the full analysis population		Study entry (Visit 1) and every 8 weeks until progressive disease or death	No