E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone receptor positive advanced breast cancer in postmenopausal women. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057654 |
E.1.2 | Term | Breast cancer female |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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%). |
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E.2.2 | Secondary objectives of the trial |
•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) and to identify exploratory marker based subsets of patients who may benefit from CP 751, 871 therapy. •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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of Study in a Member State of the European Union is defined as the time at which it is deemed that sufficient patients have been recruited and completed the study as stated in the regulatory application (ie, Clinical Study Application (CTA)) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |