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)

This study has been terminated.
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00818675
First received: January 7, 2009
Last updated: October 19, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Lead-In Ridaforolimus
Drug: Comparator: Blinded Ridaforolimus
Drug: Comparator: Blinded Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Discontinuation Phase II Trial of Ridaforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients With KRAS Mutations

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression-free survival (PFS) in the randomized population [ Time Frame: Randomization (Week 8) and every 8 weeks until progressive disease or death ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate (ORR) in the full analysis population [ Time Frame: Study entry (Visit 1) and every 8 weeks until progressive disease or death ] [ Designated as safety issue: No ]
  • Overall survival (OS) in the full analysis population [ Time Frame: From study entry (Visit 1) to death due to any cause ] [ Designated as safety issue: No ]
  • OS in the randomized population [ Time Frame: From study entry (Visit 1) to death due to any cause ] [ Designated as safety issue: No ]
  • PFS in the full analysis population [ Time Frame: Study entry (Visit 1) and every 8 weeks until progressive disease or death ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: March 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00818675

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Ariad Pharmaceuticals
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00818675     History of Changes
Other Study ID Numbers: 8669-021, 2008_599
Study First Received: January 7, 2009
Last Updated: October 19, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014