Trial Of CP-751, 871 And Erlotinib In Refractory Lung Cancer

Study Overview
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Brief Summary
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The objective of this study is to test a clinical benefit of the addition of CP 751,871 to erlotinib therapy in patients with advanced NSCLC of non adenocarcinoma histology. The primary endpoint is Overall Survival (OS).

Detailed Description
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This study was terminated on March 8, 2010 due to an analysis by an independent Data Safety Monitoring Committee (DSMC) indicating that the addition of CP-751,871 [figitumumab] to erlotinib [Tarceva] would be unlikely to meet the primary endpoint of improving overall survival when compared to erlotinib alone. This Oncology study continues as terminated, however for ethical reasons some patients, noted with resultant benefit, continue receiving treatment.

Official Title
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Randomized, Open Label, Phase 3 Trial Of Erlotinib Alone Or In Combination With CP-751,871 In Patients With Advanced Non Small Cell Lung Cancer Of Non Adenocarcinoma Histology

Conditions
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Carcinoma, Large Cell, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Carcinoma, Adenosquamous Cell

Intervention / Treatment
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* Drug: CP 751,871 (Figitumumab)
* Drug: Erlotinib
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non small cell lung cancer with a primary histology of squamous cell, large cell or adenosquamous carcinoma. At least 1 measurable lesion, as defined by RECIST. Exclusion Criteria: Primary NSCLC adenocarcinoma and its subtypes or unknown/unspecified histology. Prior Erlotinib therapy. Prior anti IGF IR based investigational therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>The CP 751,871 treatment in combination with erlotinib will be given in three week cycles. CP 751,871 (20 mg/kg) + erlotinib (150 mg/day) CP 751,871 will be administered as an IV infusion on study Days 1 and 2 in Cycle 1, and every three weeks (from Day 1) (Cycle) thereafter. | Drug: CP 751,871 (Figitumumab)<br>* CP 751,871 (20 mg/kg) will be administered as an IV infusion on study Days 1 and 2 in Cycle 1, and every three weeks (from Day 1) (Cycle) thereafter.<br>Drug: Erlotinib<br>* Erlotinib (one tablet of 150 mg/day PO).<br>|
| Active Comparator: Arm B<br>Erlotinib (one tablet of 150 mg/day PO). Erlotinib will be taken at least one hour before or two hours after the ingestion of food) | Drug: Erlotinib<br>* Erlotinib (one tablet of 150 mg/day PO). Erlotinib will be taken at least one hour before or two hours after the ingestion of food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The time from date of randomization to date of death due to any cause. For participants who were alive, overall survival was censored at the last contact. | Baseline, assessed every cycle until disease progression and then every 4 weeks until death, up to 30.65 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Time from randomization to date of first documentation of progression or death due to any cause, whichever came first. Participants last known to be alive and progression-free, who had a baseline and at least 1 on-study disease 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, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, unequivocal progression of non-target disease, or the appearance of new lesions. | Baseline, 6, 9, 12, 15, 18 weeks after randomization, thereafter assessed every 6 weeks until disease progression during treatment (or every 8 weeks until disease progression during off-treatment), up to 29.7 months | 
| Percentage of Participants With Objective Response | Percentage of participants with objective response (OR) based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. CR are defined as complete disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | Baseline, 6, 9, 12, 15, 18 weeks after randomization, thereafter assessed every 6 weeks until disease progression during treatment (or every 8 weeks until disease progression during off-treatment), up to 29.7 months | 
| Maximum Observed Plasma Concentration (Cmax) for Figitumumab |  | Cycle 1 (Day 1 [predose], Day 2 [1 hour after end of infusion] ), Cycles 2, 4, 6 (predose), Cycle 5 (predose, 1 hour after end of infusion) for figi plus erlo group; Cycles 1, 2,4 (predose) for erlo, then figi group | 
| Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab |  | Cycle 1 (Day 1 [predose], Day 2 [1 hour after end of infusion] ), Cycles 2, 4, 6 (predose), Cycle 5 (predose, 1 hour after end of infusion) for figi plus erlo group; Cycles 1, 2,4 (predose) for erlo, then figi group | 
| Percentage of Participants Reporting Positive for Total Anti-drug Antibodies (ADA) | ADAs are immunogenicity indicators to figitumumab. Participants reporting positive for ADAs are indicated by an endpoint titer of no less than 6.64. | Cycles 1, 2, 4 (predose), End of Treatment ([EOT] 21-28 days after last dose), about 150 days after last figi dose for figi plus erlo group; Cycles 1, 2, 4 (predose), EOT, about 150 days after last figi dose for erlo, then figi group | 
| Counts of Circulating Tumor Cell (CTC) Expressing Positive Insulin-Like Growth Factor 1 Receptor (IGF-1R) |  | Baseline, Cycle 2 Day 1 (predose) and EOT (21-28 days after last dose) | 
| Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility at Cycles 2, 3, Then Every Other Cycle and EOT (21-28 Days After Last Dose) | EQ-5D is a 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. 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 -0.594 to 1.000; higher score indicates a better health state. | Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every other cycle and EOT (21-28 days after last dose) | 
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) at Cycles 2, 3, and Then Every Odd Cycle Starting With Cycle 5 and EOT (21-28 Days After Last Dose) | EORTC QLQ-C30 includes 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 use 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. | Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every odd cycle starting with Cycle 5 and EOT (21-28 days after last dose) | 
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) Score at Cycles 2, 3, and Then Every Odd Cycle Starting With Cycle 5, and EOT (21-28 Days After Last Dose) | QLQ-LC13 consists 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 comprise 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. | Baseline (Cycle 1 Day 1 predose), Cycles 2, 3 (Day 1), every odd cycle starting with Cycle 5 and EOT (21-28 days after last dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IGR-1R, Non small cell lung cancer, CP-751, 871, Figitumumab