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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00596830
First received: January 3, 2008
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Carcinoma, Squamous Cell
Carcinoma, Adenosquamous
Carcinoma, Large Cell
Carcinoma, Non-Small-Cell Lung
Drug: CP-751,871 (Figitumumab)
Drug: Carboplatin
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline until death, assessed monthly after end of treatment, up to 30 months ] [ Designated as safety issue: No ]
    Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 681
Study Start Date: April 2008
Study Completion Date: September 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Patients in Arm A will receive CP-751, 871 in combination with paclitaxel and carboplatin intravenously every 21 days for up to six cycles.`
Drug: CP-751,871 (Figitumumab)
CP 751,871 is a potent and selective fully human monoclonal antibody against the insulin like growth factor 1 receptor (IGF-1R). Patients in Arm A will receive CP-751, 871 intravenously every 21 days for up to six cycles.
Drug: Carboplatin
Carboplatin is a standard chemotherapeutic agent used in patients with lung cancer. Patients in Arm A will receive carboplatin intravenously every 21 days for up to six cycles.
Drug: Paclitaxel
Paclitaxel is a standard chemotherapeutic agent used in patients with lung cancer. Patients in Arm A will receive paclitaxel intravenously every 21 days for up to six cycles.
Active Comparator: B
Patient in Arm B will receive paclitaxel and carboplatin intravenously every 21 days for up to six cycles.
Drug: Carboplatin
Carboplatin is a standard chemotherapeutic agent used in patients with lung cancer. Patient in Arm B will receive carboplatin intravenously every 21 days for up to six cycles.
Drug: Paclitaxel
Paclitaxel is a standard chemotherapeutic agent used in patients with lung cancer. Patient in Arm B will receive paclitaxel intravenously every 21 days for up to six cycles.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of non small cell lung cancer with a primary histology of predominantly squamous cell, large cell or adenosquamous carcinoma.
  • Advanced NSCLC with documented Stage IIIB (with pleural effusion) or Stage IV or recurrent disease.
  • No prior systemic treatment for NSCLC, except for adjuvant chemotherapy. Adjuvant chemotherapy must have completed for greater than or equal to 12 months prior to randomization.
  • Prior surgery or radiation therapy is permitted if completed at least 3 weeks prior to randomization and all acute toxicities have resolved.
  • ECOG performance status (PS) 0 or 1.

Exclusion Criteria:

  • Patients with symptomatic central nervous system (CNS) metastases are not permitted.
  • Patients requiring chronic steroid use or patients with uncontrolled diabetes are not permitted.
  • Patients with other active cancer types are not permitted.
  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: NCT00596830

  Show 280 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00596830     History of Changes
Other Study ID Numbers: A4021016
Study First Received: January 3, 2008
Results First Received: September 25, 2013
Last Updated: December 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
IGF-1R inhibitor
Non-small-cell lung carcinoma
CP-751
871

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Adenosquamous
Carcinoma, Large Cell
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 27, 2014