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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-005573-21-NL
• Date of registration: 06/03/2008
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 30/07/2008
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005573-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, Italy, Netherlands, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.Females >18 years of age.
2.Histologically or cytologically confirmed adenocarcinoma of the breast, either metastatic, or locally advanced Stage IIIB, or loco-regional recurrent and not amenable to curative treatment with surgery or radiotherapy.
3.Measurable or evaluable disease (See Appendix 7).
4.Patients must be postmenopausal. Postmenopausal is defined by any of the following:
•Woman >60 yrs
•Woman of age 45-59 yrs with spontaneous amenorrhea for >1 year prior to randomization
•Woman of age 45-59 yrs with cessation of menses duration <1 year or secondary to hysterectomy AND with FSH levels pre-randomization clearly in the laboratory postmenopausal range (or >34.4 IU/L if institutional range is not available)
•Woman of age 45-59 yrs previously on HRT who discontinued HRT at breast cancer diagnosis and who has FSH level pre-chemotherapy or pre-randomization clearly in the laboratory postmenopausal range (or >34.4 IU/L if institutional range is not available)
•Bilateral oophorectomy
•Ovarian ablation by radiotherapy confirmed by FSH level in the postmenopausal range
5.Evidence of hormone sensitivity (ER+ and/or PR+) of primary or secondary tumor tissue. Positivity is defined either as =10 fmol of H3 -estrogen binding per mg of cytosol protein for dextran coated charcoal and sucrose density methods or =0.10 fmol of H3 -estrogen binding per mg of DNA for IF/EIA technique. In case of use of immunohistochemistry, the report should mention positive receptor status according to the standards of the laboratory.
6.Must be appropriate to receive endocrine therapy as treatment for advanced disease.
7.Prior radiotherapy (more than 3 weeks prior to randomization) is allowed. A measurable or evaluable lesion that has been previously irradiated will be evaluated only after it is considered to have progressed before randomization. Patients must have recovered from all acute radiation toxicities.
8.Concurrent bisphosphonate treatment is allowed if established 2 weeks prior to randomization. Patients on bisphosphonates at randomization must be kept on bisphosphonate during the study (see also Concomitant Medications Section).
9.Patients must have an ECOG performance status 0, 1, or 2 (See Appendix 5).
10.Patients must have adequate hematologic function as defined by:
•ANC =1500/mm3
•Platelets =100000/mm3
•Hemoglobin =8.5 g/dL
11.Patients must have adequate renal and liver function as defined by:
•Serum creatinine and serum bilirubin level 1.5 x ULN
•ALT and AST =2.5 x ULN (or =5 in case of liver metastasis).
12.Serum calcium =11.6 mg/dL (or =2.75 mmol/L).
13.Written and voluntary informed consent understood, signed and dated.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Male patients.
2.Presence of life threatening metastatic disease defined as extensive (more than one third of the organ) hepatic involvement, any past or present brain or leptomeningeal involvement, or symptomatic pulmonary lymphangitic spread (>50% lung involvement). Patients with discrete pulmonary parenchymal metastases will not be excluded as long as their respiratory function is not compromised.
3.Presence of unevaluated central nervous system (CNS) symptoms suggestive of brain metastases within 2 weeks prior to randomization. CNS symptoms must be evaluated by CT or MRI scan.
4.Patients who are highly symptomatic from their breast cancer, or who require urgent palliative chemotherapy, as decided by their treating physician.
5.Adjuvant/neoadjuvant therapy with aromatase inhibitors within 12 months of randomization.
6.Adjuvant/neoadjuvant tamoxifen within 2 weeks of randomization.
7.Adjuvant/neoadjuvant chemotherapy (excluding anthracycline) within 4 weeks of randomization.
8.Adjuvant/neoadjuvant anthracycline and/or trastuzumab therapy within 6 months of randomization.
9.Prior anti IGF 1R investigational therapy.
10.Surgery within 4 weeks prior to randomization or not fully recovered from side effects of previous procedures.
11.Any previous chemotherapy, hormonal (eg, tamoxifen, SERMs, aromatase inhibitors, LHRH agonists, ovariectomy, radiocastration) or targeted therapy, including immunotherapy, for advanced disease.
12.Patients with a known hypersensitivity to exemestane or to any of its excipients.
13.Patients with a known hypersensitivity to antibody therapy.
14.History of malignancy other than breast cancer within 5 years before study start with the exception of appropriately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin.
15.A serious uncontrolled medical disorder or active infection that would impair the ability to receive study treatment.
16.Significant active cardiac disease including: uncontrolled high blood pressure (ie, systolic blood pressure =180 mm Hg, diastolic blood pressure =95 mm Hg), unstable angina, deep venous thrombosis, pulmonary embolism, cerebro vascular attack, valvular disease, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias.
17.Use of high dose corticosteroids within 2 weeks prior to randomization (=100 mg prednisone per day or =40 mg dexamethasone per day).
18.Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
19.Any other major illnesses that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Hormone receptor positive advanced breast cancer in postmenopausal women.
MedDRA version: 9.1 Level: LLT Classification code 10057654 Term: Breast cancer female

Intervention(s)

Product Name: CP-751,871
Product Code: CP-751,871
Pharmaceutical Form: Intravenous infusion

Trade Name: Aromasin
Product Name: Aromasin
Product Code: Exemestane
Pharmaceutical Form: Coated tablet

Primary Outcome(s)

Main Objective: To compare the efficacy, in terms of progression free survival (PFS), of CP 751,871 in combination with exemestane vs. exemestane alone as first line treatment of postmenopausal women with hormone-dependent advanced breast cancer.

Secondary Objective: • To define the efficacy, in terms of clinical benefit (CR+PR+ [SD=6 months]) of exemestane alone and in combination with CP 751,871.
• To assess the safety and tolerability of multiple doses of CP 751,871 in combination with exemestane.
• To define the proportion of patients with measurable circulating tumor cells that express surface IGF 1R (CTCs IGF-1R positive) at study entry.
• To evaluate the effect of CP-751,871 therapy on serum markers relevant to the IGF 1R pathway (such as: hGH, insulin, IGF-1, IGF-2, IGF-BP and ErbB-1,2).
• To evaluate the PK of CP 751,871 given in combination with exemestane.
• To test for the occurrence of HAHA response to CP 751,871.
• To examine the Patient Reported Outcomes of Health-Related Quality of Life (PROs of HRQoL; hereafter referred to as HRQoL) of CP 751,871 in combination with exemestane vs. exemestane alone.

Primary end point(s): PFS

Secondary ID(s)

2006-005573-21-BE

A4021004