Clinical Trial: Study of Maintenance Temozolomide Versus Observation in Stable or Responding Stage III/IV Non-Small Cell Lung Cancer Patients (Study P05146)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Randomized Phase 2 Study of Maintenance Temozolomide Versus Observation in Stable or Responding Stage III/IV Non-Small Cell Lung Cancer Patients

Brief Summary: The main objective of this study is to investigate whether administration of maintenance temozolomide following standard treatment could possibly prevent or delay the onset of brain metastases in patients with controlled non-small cell lung cancer (NSCLC).

Detailed Summary: This is a Phase 2, open-label, randomized, multicenter study of maintenance temozolomide versus observation in subjects with stable or responding stage III/IV NSCLC to be conducted in conformance with Good Clinical Practices. Subjects will be randomly assigned to a study drug (temozolomide) or observation arm. The study drug will be administered at a dose of 75 mg/m^2 PO daily for 21 consecutive days, followed by a 7-day rest period, until progression or up to a maximum of 6 cycles, whichever occurs first. Subjects completing 6 cycles of treatment will be followed up for incidence of brain metastasis for up to 2 years, or until progression.
Sponsor: Merck Sharp & Dohme Corp.

Current Primary Outcome: Number of Participants Who Had Brain Metastases [ Time Frame: Up to 12 months (as measured from day 1 of cycle 1 of standard first-line systemic chemotherapy) ]

Original Primary Outcome: Incidence of brain metastases, according to MRI of the brain, at 12 months (as measured from day 1 of cycle 1 of standard systemic chemotherapy) [ Time Frame: At 12 months (as measured from day 1 of cycle 1 of standard systemic chemotherapy) ]

Current Secondary Outcome:

• Time to Radiological Central Nervous System (CNS) Progression [ Time Frame: from Cycle 1 Day 1 of Standard First Line Systemic Therapy to radiological progression or the last known CNS progression-free date ]

  Defined as CNS progression as measured by MRI.

  Time to CNS progression was analyzed using the Kaplan-Meier method.

• Time to Progression [ Time Frame: from Cycle 1 Day 1 of Standard First Line Systemic Therapy to progression or up to 6 cycles (168 days) of study treatment ]

  The time to progression (per response evaluation criteria in solid tumors [RECIST]) was analyzed using the Kaplan-Meier method.

  Definitions of response per RECIST:

  Complete Response (CR): Disappearance of all target lesions.

  Partial Response (PR): A decrease of at least 30% in the sum of the longest

  diameter of target lesions.

  Progressive Disease (PD): An increase of at least 20% in the sum of the longest

  diameter of target lesions.

  Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

• Overall Survival [ Time Frame: from Cycle 1 Day 1 of Standard First Line Systemic Therapy to the last time of follow-up ]
  The overall survival was analyzed using the Kaplan-Meier method.
• Number of Participants With Brain Metastases at First Progression [ Time Frame: from Cycle 1 Day 1 of Standard First Line Systemic Therapy to the last time of follow-up (up to 6 cycles (168 days) of study treatment) ]
  Brain Metastases were defined as radiological evidence of brain metastases on MRI.
• Cancer-related Quality of Life (QoL) as Assessed by The European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire C30 Version 3.0 (QLQ-C30), and the EORTC Lung Cancer Module (QLQ-LC13) [ Time Frame: from Cycle 1 Day 1 of Standard First Line Systemic Therapy to the last time of follow-up (up to 6 cycles (168 days) of study treatment) ]
  The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Scores range from 0 -100. For functional and global QoL scales, higher scores mean a better level of function. For symptom-oriented scales, a higher score means more severe symptoms and a decrease in QoL. The EORTC QLQ-LC13 is a 13-item questionnaire developed to supplement the EORTC QLQ-C30 in lung cancer patients. It has a score range 0-100 with higher scores representing an increase in symptoms.
• Tolerability of Maintenance Temozolomide [ Time Frame: from Cycle 1 Day 1 of Standard First Line Systemic Therapy to the last time of follow-up (up to 6 cycles (168 days) of study treatment) ]
  Tolerability was defined as number of participants with any adverse event leading to study discontinuation and/or study drug discontinuation.

Original Secondary Outcome:

• Time to radiological or clinical CNS progression; Time to progression; incidence of brain metastases at first progression [ Time Frame: At progression or last known progression-free date ]
• Overall survival [ Time Frame: At initial follow-up, 30 days after final dose of study drug; then every 12 weeks (+/-1 week) and at 12 months (+/-1 week) from Day 1 Cycle 1 ]
• Cancer-related QoL assessment [ Time Frame: Before the first treatment, at the end of each treatment cycle, and at the end of treatment ]
• Tolerability of Maintenance Temozolomide [ Time Frame: Before the first treatment, at the end of each treatment cycle, at the end of treatment, and 30 days after the end of treatment ]

Dates:
Date Received: February 29, 2008
Date Started: March 2008
Date Completion:
Last Updated: August 26, 2015
Last Verified: August 2015