Study Of CP-751,871 In Combination With Exemestane In Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer

Study Overview
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Brief Summary
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To test the efficacy of CP-751,871 combined with exemestane in the treatment of postmenopausal patients with hormone positive advanced breast cancer

Official Title
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A Two-arm Randomized Open Label Phase 2 Study Of Cp-751,871 In Combination With Exemestane Versus Exemestane Alone As First Line Treatment For Postmenopausal Patients With Hormone Receptor Positive Advanced Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: CP-751,871
* Drug: exemestane
* Drug: exemestane
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women with a diagnosis of hormone receptor positive advanced breast cancer HbA1c <5.7% Exclusion Criteria: Previous treatment for advanced disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: 1<br>CP-751,871 + exemestane Treatment until progression or toxicity | Drug: CP-751,871<br>* CP-751,871 given at 20 mg/kg IV on day 1 of each 21 day cycle.<br>Drug: exemestane<br>* Exemestane given at 25 mg orally once a day.<br>Drug: Fulvestrant<br>* Used for salvage therapy and administered according to the local label and standard clinical practice.<br>|
| Active Comparator: 2<br> | Drug: exemestane<br>* Exemestane given at 25 mg orally once a day. Treatment until progression or toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20 percent [%] increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by Response Evaluation Criteria in Solid Tumors [RECIST]); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% confidence interval (CI) is based on the Brookmeyer and Crowley method. | Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months | 
| PFS in Participants With Hemoglobin A1c (HbA1c) Less Than (<) 5.7% at Baseline | PFS was calculated from the time of randomization to either progression of disease, death, or treatment discontinuation because of unsatisfactory therapy results (such as global deterioration of health status). Disease progression was defined as 1 or more of the following: radiographic progression (20% increase in measurable lesions, appearance of new lesions or unequivocal progression of evaluable lesions as defined by RECIST); occurrence of new pleural/pericardial effusions or ascites confirmed by positive cytology; persistent hypercalcemia requiring more than 2 IV treatments with bisphosphonates; intervention for any cancer-related events (radiations, surgery) or new symptoms related to tumor growth requiring participant discontinuation; development of brain metastasis; or death for any cause. Median PFS was estimated from the Kaplan-Meier curve. 95% CI is based on the Brookmeyer and Crowley method. | Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) Maintained for at Least 6 Months | Objective responses were defined using RECIST as CR: disappearance of all target and nontarget lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. Nontarget lesions may persist provided there is no unequivocal progression in these lesions. SD: measurements demonstrating neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progressive disease (PD) during the first 6 weeks after the start of treatment taking as reference the smallest sum LD since the treatment started. During this time, nontarget lesions may persist provided there is no unequivocal progression in these lesions. | Baseline, Day 1 of Cycles 2 and 4 and then Day 1 of every 3rd cycle starting at Cycle 7 up to 60 months | 
| Maximum Plasma Concentration of CP-751,871 |  | Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871 | 
| Minimum Plasma Concentration of CP-751,871 |  | Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871 | 
| Area Under the Concentration Time Curve From Time 0 to the Last Time Point With Quantifiable Concentration |  | Predose on Day 1 at Cycles 1, 2, 4, and 5 and 150 days post last dose of CP-751,871 and for salvage therapy, at Day 1 and 150 days post last dose of CP-751,871 | 
| Number of Participants With Negative Human Anti-Human Antibodies (HAHAs) | Negative human anti-human antibodies were defined as <6.64 | Predose on Day 1 of Cycle 1 and at 150 days post last CP-751,871 infusion | 
| Percentage of Participants With Circulating Tumor Cells Expressing Insulin-Like Growth Factor 1 Receptor (IGF-IR) |  | Predose on Day 1 of Cycle 1 | 
| Percentage of Participants With Serum Markers Relevant to the IGF-1R Pathway |  | Predose on Day 1 of Cycles 1 and 4 and at end of treatment prior to beginning salvage therapy | 
| European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30 (QLQ-C30) Scores | 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 equals (=) better level of functioning or greater degree of symptoms. | Predose on Day 1 of each cycle, at the end of treatment and at follow-up, up to 60 months | 
| EORTC QLQ Breast Cancer Module (BR23) Scores | EORTC-QLQ-BR23: included functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions used 4-point Likert scale (1 â€˜Not at Allâ€™ to 4 â€˜Very Muchâ€™). Scores averaged and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems. Change from baseline=Cycle/Day score minus baseline score. | Predose on Day 1, at end of treatment, and at Follow-up, up to 60 months |