Clinical Trial: Carboplatin And Paclitaxel With Or Without CP-751, 871 (An IGF-1R Inhibitor) For Advanced NSCLC Of Squamous, Large Cell And Adenosquamous Carcinoma Histology

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

Official Title: Randomized, Open Label, Phase III Trial Of CP- 751,871 In Combination With Paclitaxel And Carboplatin Versus Paclitaxel And Carboplatin In Patients With Non Small Cell Lung Cancer

Brief Summary: Determine whether the addition of CP- 751,871 in combination with paclitaxel plus carboplatin prolongs survival in patients with locally advanced (Stage IIIB with pleural effusion) or metastatic (Stage IV or recurrent) NSCLC of non adenocarcinoma histology.

Detailed Summary: The study was discontinued on December 29, 2009 due to an analysis by an independent Data Safety Monitoring Committee indicating that the addition of CP-751,871 [figitumumab] to paclitaxel plus carboplatin would be unlikely to meet the primary endpoint of improving overall survival compared to paclitaxel plus carboplatin alone. The DSMC recommendation to terminate the trial was based on futility, not on specific safety concerns; however, the DSMC recommended to investigate hyperglycemia as a potential contributor to the morbidity of the patients.
Sponsor: Pfizer

Current Primary Outcome: Overall Survival (OS) [ Time Frame: Baseline until death, assessed monthly after end of treatment, up to 30 months ]

Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.


Original Primary Outcome: Overall Survival (OS) [ Time Frame: 3 years ]

Current Secondary Outcome:

  • Progression-Free Survival (PFS) [ Time Frame: At baseline, every 6 weeks until radiological disease progression or the participant begins a subsequent anticancer therapy, up to 22.7 months. ]
    PFS was defined as the time from randomization to first progression or death due to any cause, whichever came first. Participants last known to be alive and progression-free, with baseline and >=1 on-study assessment, were censored at last disease assessment verifying lack of progression. Progression was determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (20% increase in the sum of target lesions' longest diameter over nadir, unequivocal progression of non-target disease, or appearance of new lesions).
  • Percentage of Participants With Objective Response (OR) [ Time Frame: At baseline, every 6 weeks until radiological disease progression has been documented or the participant begins a subsequent anticancer therapy, up to 22.7 months ]
    Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response(PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as complete disappearance of all target lesions and non-target disease. No new lesons. PR defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.
  • European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Day 1 of every cycle (3-week cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months ]
    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
  • European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score [ Time Frame: Day 1 of every cycle (3-week cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months ]
    QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
  • Euro Quality of Life (EQ-5D)- Health State Profile Utility Score [ Time Frame: Day 1 of every cycle (3-weeks cycle), every 3 weeks during maintenance phase and at the End of Treatment Visit, assessed up to 37.4 months ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range of -0.594 to 1; higher score indicates a better health state.
  • Maximum Observed Plasma Concentration (Cmax) for Figitumumab [ Time Frame: Cycle 1, Day 1 (predose and 1 hour after end of infusion); Day 1 of Cycles 2, 4, 6 (predose); Cycle 5 Day 1 (predose, 1 hour after end of infusion); 28 days and 150 days after the last figi dose ]
  • Minimum Observed Plasma Trough Concentration (Cmin)for Figitumumab [ Time Frame: Cycle 1, Day 1 (predose and 1 hour after end of infusion); Day 1 of Cycles 2, 4, 6 (predose); Cycle 5 Day 1 (predose, 1 hour after end of infusion); 28 days and 150 days after the last figi dose ]
  • Number of Participants With Total Anti-drug Antibodies (ADA) [ Time Frame: Cycles 1, 2, and 4 (predose); 28 days and 150 days after the last figi dose ]
    ADAs are immunogenicity indicators to figitumumab. Participants reporting positive for ADAs are indicated by an endpoint titer of no less than 6.64.
  • Change From Baseline in Serum Insulin Growth Factor 1 (IGF1) Levels [ Time Frame: Cycles 1 and 4 (predose) and at end of treatment ]


Original Secondary Outcome:

  • Progression Free Survival (PFS) [ Time Frame: 2.5 years ]
  • Overall safety profile [ Time Frame: 3 years ]
  • Patient reported outcomes (PROs) [ Time Frame: 3 years ]
  • Pharmacokinetics of CP- 751,871 [ Time Frame: 3 years ]
  • Anti drug antibody occurrence [ Time Frame: 3 years ]
  • Change in serum IGF1 levels [ Time Frame: 3 years ]
  • Overall objective response rate (ORR) [ Time Frame: 3 years ]


Information By: Pfizer

Dates:
Date Received: January 3, 2008
Date Started: April 2008
Date Completion:
Last Updated: December 11, 2013
Last Verified: December 2013