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

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

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

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: CP-751,871; Drug: exemestane; Drug: exemestane; Drug: Fulvestrant

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, X5004BAL
    • Hospital Italiano Cordoba
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, B1902CMV
      • Breast clinica de la mama
    • La Plata, Buenos Aires, Argentina, B1902 CMV
      • Policlinica Privada Site La Plata S.A.
    • La Plata, Buenos Aires, Argentina, B1902CMV
      • Policlinica Privada Site
    • La Plata, Buenos Aires, Argentina
      • Policlinica Privada Site La Plata S. A.
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CVD
      • Instituto de Investigaciones Clinicas
    • Rosario, Santa Fe, Argentina, S2000DSK
      • Centro Oncologico Rosario
    • Rosario, Santa Fe, Argentina, S2000KZE
      • Centro Oncologico de Rosario
  • Santa Fé
    • Rosario, Santa Fé, Argentina, S2000KZE
      • Centro Oncologico
• Belgium
  • Leuven, Belgium, 3000
    • UZ Gasthuisberg
  • Leuven, Belgium, 3000
    • UZ Gasthuisberg, Medische Oncologie
  • Wilrijk, Belgium, 2610
    • Oncologisch Centrum GZA
• Brazil
  • Porto Alegre, Brazil, 90610-000
    • Centro de Pesquisa em Oncologia - CPO
  • Rio De Janeiro, Brazil, RJ 20230 - 130
    • Instituto Nacional do Câncer
  • QC
    • Montreal, QC, Brazil, H3T 1E2
      • Jewish General Hospital
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20560-120
      • Instituto Nacional Do Câncer - Inca
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital São Lucas da PUCRS
    • Porto Alegre, RS, Brazil, 90430-090
      • Clínica de Oncologia de porto Alegre Sociedade Simples ltda.
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital São Lucas da PUCRS
  • Rio de Janeiro
    • Santo Cristo, Rio de Janeiro, Brazil, RJ 20220-410
      • Instituto Nacional de Cancer - HCII
  • SP
    • Sao Paulo, SP, Brazil, 05403-900
      • Hospital Das Clinicas Da Faculdade De Medicina Da Universidade De Sao Paulo Instituto Central
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B. Davis - Jewish General Hospital
• Italy
  • Milano, Italy, 20141
    • Dipartimento di Medicina, Divisione di Oncologia Medica, Istituto Europeo di Oncologia
  • Napoli, Italy, 80131
    • Divisione di Oncologia
  • Padova, Italy, 35128
    • Uo Oncologia Medica 2 Regione Del Veneto Istituto Oncologico Veneto IRCCS Ospedale Busonera
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU University Medical Center
• Sweden
  • Malmo, Sweden, 205 02
    • Malmö University Hospital
• United Kingdom
  • London, United Kingdom, W6 8RF
    • Imperial College Healthcare NHS Trust - Charing Cross Hospital
  • London, United Kingdom, W2 1NY
    • St Mary's Hospital NHS Trust
• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center
    • La Jolla, California, United States, 92037
      • UCSD Medical Center - La Jolla
    • San Diego, California, United States, 92103
      • UCSD Medical Center - Hillcrest
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-3017
      • Washington Cancer Institute (WCI) at Washington Hospital Center (WHC)
  • Florida
    • Davie, Florida, United States, 33328
      • Florida Cancer Research Institute
    • Plantation, Florida, United States, 33324
      • Florida Cancer Research Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Central Baptist Hospital
    • Lexington, Kentucky, United States, 40503
      • Lexington Oncology Associates
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Hematology/Oncology, PSC
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Bringham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute (DFCI)
    • Boston, Massachusetts, United States, 2215
      • Dana-Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Medical Center-Fairview, Riverside Campus
  • North Carolina
    • Burlington, North Carolina, United States, 27215-8700
      • Alamance Regional Medical Center - Cancer Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University School of Medicine
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center - Morris Cancer Center Clinics
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center- Department of Medicine Oncology
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center-Duke Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246-2006
      • Texas Oncology - PA Collins Building 5th Floor
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine (BCM)
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Breast Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care
    • Burlington, Vermont, United States, 05401-1473
      • Fletcher Allen Healthcare
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Hospital MCHV Campus
    • Burlington, Vermont, United States, 05401
      • Pharmacist, Investigational Drug Service
    • Burlington, Vermont, United States, 05405
      • Fletcher Allen Healthcare
    • Burlington, Vermont, United States, 5401
      • Fletcher Allan Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women with a diagnosis of hormone receptor positive advanced breast cancer
• HbA1c <5.7%

Exclusion Criteria:

• Previous treatment for advanced disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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 ‘Not at All’ to 4 ‘Very Much’). 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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: September 5, 2006
• First Submitted That Met QC Criteria: September 6, 2006
• First Posted (Estimate): September 7, 2006

Study Record Updates

• Last Update Posted (Estimate): October 28, 2015
• Last Update Submitted That Met QC Criteria: October 6, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant; Exemestane
• Other Study ID Numbers: A4021004; 2006-005573-21 (EudraCT Number)