Study comparing exemestane alone compared to exemestane + CP-751,871 as initial therapy for estrogen receptor positive advanced breast cancer.

• Register: EUCTR
• Last refreshed on: 22 August 2016
• Main ID: EUCTR2006-005573-21-BE
• Date of registration: 19/12/2006
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: Study comparing exemestane alone compared to exemestane + CP-751,871 as initial therapy for estrogen 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: 26/01/2007
• Target sample size: 218
• 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 Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Brazil, Canada, Italy, Netherlands, Sweden, United Kingdom

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study, unless there is compelling reason which is to be agreed by the investigator and sponsor prior to randomization:
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.
4. Patients must be postmenopausal. Postmenopausal is defined by any of the
following:
• Woman = / > 60 yrs;
• Amenorrhea for = / >5 years prior to randomization;
• 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 according to the criteria of the participating Institution.
6. Must be appropriate to receive endocrine therapy as treatment for advanced disease.
7. Prior palliative radiotherapy 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. Patients must have HbA1c<5.7%.
9. Concurrent bisphosphonate treatment is allowed but not required. Patients on
bisphosphonates at randomization must be kept on bisphosphonate during the study.
10. Patients must have an ECOG performance status 0, 1, or 2 ).
11. Adequate recovery from major surgery prior to randomization. Wound healing must be complete.
12. Patients must have adequate hematologic function as defined by:
• ANC = / >1500/mm3;
• Platelets = / >100000/mm3;
• Hemoglobin = / >8.5 g/Dl.
13. 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).
14. Serum calcium < / = 11.6 mg/dL (or < / = 2.75 mmol/L).
15. Written and voluntary informed consent understood, signed and dated.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 109
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 109

Exclusion criteria:
Patients presenting with any of the following will not be included in the study, unless there is compelling reason which is to be agreed by the investigator and sponsor prior to randomization:
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 steroidal aromatase inhibitors within 12 months of randomization.
6. Adjuvant/neoadjuvant tamoxifen within 2 weeks of randomization.
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. Prior therapy for metastatic/advanced disease including, but not limited to,
chemotherapy, hormonal (eg, tamoxifen, SERMs, LHRH agonists, ovariectomy,
radiocastration) or targeted therapy, including immunotherapy. Prior AI is allowed if
less than 4 weeks prior to randomization.
11. Patients with a known hypersensitivity to exemestane or to any of its excipients.
12. Patients with a known hypersensitivity to antibody therapy.
13. 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.
14. A serious uncontrolled medical disorder or active infection that would impair the
ability to receive study treatment.
15. Any history of unstable angina, myocardial infarction or symptomatic congestive
heart failure. Significant active cardiac disease including: uncontrolled high blood pressure (ie, systolic blood pressure =180 mm Hg, diastolic blood pressure =95 mm Hg), deep venous thrombosis, pulmonary embolism, endocarditis, cerebro-vascular attack, or valvular disease within the previous 6 months. Patients with a requirement for inotropic support or serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) within 3 years prior to screening. Patients requiring the use of pacemakers or implanted defibrillators.
16. Use of high dose corticosteroids within 2 weeks prior to randomization
(=100 mg prednisone per day or = / > 40 mg dexamethasone per day).
17. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
18. Any other major illnesses or laboratory abnormality 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

Therapeutic area: Diseases [C] - Cancer [C04]

Hormone receptor positive advanced breast cancer in postmenopausal women.
MedDRA version: 14.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: CP-751,871
Product Code: CP-751,871
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: figitumumab
CAS Number: none
Current Sponsor code: CP-751,871
Other descriptive name: none
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Aromasin
Product Name: Aromasin
Product Code: Exemestane
Pharmaceutical Form: Coated tablet
INN or Proposed INN: exemestane
CAS Number: 633-35-2
Other descriptive name: irreversible, steroidal aromatase inactivator
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 25-

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 with low risk for the development of diabetes (Hb A1C<5.7%).

Timepoint(s) of evaluation of this end point: PFS follow-up will end during fourth quarter of 2011

Primary end point(s): PFS

Secondary Objective: •Define the efficacy, in terms of clinical benefit (CR+PR+ [SD=6 months]) of exemestane alone and in combination with CP-751,871.
•Assess the safety and tolerability of multiple doses of CP-751,871 in combination with exemestane.
•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) and to identify exploratory marker based subsets of patients who may benefit from CP-751, 871 therapy.
•Evaluate the PK of CP-751,871 given in combination with exemestane.
•Test for the occurrence of HAHA response to CP-751,871. The Sponsor has collected ample HAHA [also known as anti-drug antibody (ADA)]. For a summary of these results, please refer to the 2011 Figitumumab Investigator Brochure. Revised objective: Figitumumab HAHA samples and corresponding figitumumab plasma concentration (PK) samples will only be collected if ADA formation is clinically suspected (e.g. hypersensitivity reaction).

Secondary Outcome(s)

Secondary end point(s): • Clinical benefit (CR + PR + [SD =6 months])
• Safety and tolerability
• PK parameters of CP-751,871
• HAHA
• CTCs expressing IGF-1R
• Serum markers relevant to CP-751,871 therapy
• HRQoL

Timepoint(s) of evaluation of this end point: Main Secondary endpoint: Safety;
Safety follow-up will continue indefinitely until all patients have either died or have completed the 150 day follow up period after the last dose of figitumumab.

Secondary ID(s)

A4021004

Source(s) of Monetary Support

Pfizer Inc.