E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Female patients with operable breast cancer, fulfilling the following criteria. |
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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 | 10006204 |
E.1.2 | Term | Breast carcinoma |
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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 |
First Study Part: To evaluate the effect of R1507 treatment on IGF-1R expression in breast cancer cells. Second Study Part: To define and confirm a PK/PD threshold effect of R1507 by assessing lower dose levels
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of R1507 treatment in breast cancer cells: on p-AKT level on Ki67 index on apoptotic index •To correlate R1507 PK parameters in serum with biologic changes in tumor tissue •To evaluate the safety and tolerability of R1507 in patients with breast cancer
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female only 2. Age ≥ 18 years 3. Able to comply with the protocol 4. Histological diagnosis of invasive breast cancer 5. Operable breast cancer 6. Availability of liquid nitrogen-stored breast tissue samples from the breast cancer diagnostic biopsy 7. Written informed consent (Informed Consent document to be approved by the institution’s Independent Ethics committee [IEC]) for study participation including use of diagnostic breast lesion biopsy and excised tissue at definitive breast surgery, obtained from all subjects prior to any study specific screening 8. ECOG Performance Status of 0 or 1 9. Life expectancy >4 months 10. INR ≤ 1.5 and APTT ≤ 1.5 x ULN for the reference lab 11. Adequate bone marrow function as evidenced by: - ANC ≥1500/mm3 - Platelet count ≥ 100,000/mm3 - Hemoglobin ≥ 9.0 g/dL (after transfusion, if needed) 12. Adequate renal function as evidenced by serum creatinine ≤1.5 x ULN for the reference lab 13. Adequate hepatic function as evidenced by: - Serum albumin ≥ 2.5 mg/dL - Serum total bilirubin ≤2.0 mg/dL - ALT/AST≤ 2.5 x ULN for the reference lab - Alkaline phosphatase ≤2.5 x ULN for the reference lab 14. HbA1c ≤ 7% 15. Negative pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause
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E.4 | Principal exclusion criteria |
1. Evidence of metastatic disease 2. Prior hormonal or systemic therapy for breast cancer 3. Prior treatment with an agent targeting the IGF-1R pathway 4. Inflammatory breast cancer 5. Patients with history of organ (including bone marrow) transplantation 6. Major surgical procedure or significant traumatic injury within 14 days prior to start of study treatment 7. Patients who have known hypersensitivity to any of the components of R1507 or who have had prior hypersensitivity reactions to monoclonal antibodies 8. Patients who have received investigational agent therapy within 30 days or a period of 5 half-lives (whichever is longer) of the investigational agent therapy in question (or longer, at the discretion of the investigator) prior to the first scheduled day of dosing (investigational agent therapy is defined as treatment for which there is currently no regulatory authority approved indication) 9. Patients who are receiving concurrent radiotherapy or who have received radiotherapy for current active disease. 10. Patients who are receiving concurrent antibody or immunotherapy (i.e., interferon-alpha, interferon-beta, interleukin-2, etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, or efalizumab) or have received antibody or immunotherapy within 4 weeks prior to receipt of study drug 11. Administration of high doses of systemic corticosteroids High dose is considered as > 20 mg of dexamethasone a day (or equivalent) for > 7 consecutive days 12. Patients who are receiving concurrent warfarin anticoagulant therapy 13. Any disease [including psychotic/mental disorders, drug abuse, active infection, uncontrolled hypertension, clinically significant cardiovascular disease [for example CVA (≤ 6 months before the start of treatment), myocardial infarction (≤ 6 months before the start of treatment), unstable angina, NYHA ≥ Grade 2 CHF, unstable arrhythmia requiring medication], hepatic, renal or metabolic disease (including uncontrolled diabetes mellitus), metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications 14. Uncontrolled CNS disease (e.g., seizures not controlled with standard medical therapy) 15. Women of childbearing potential (WCBP) (<2 years after last menstruation) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) 16. Known HIV or Hepatitis B or C (active, previously treated or both)
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E.5 End points |
E.5.1 | Primary end point(s) |
The overall percent of evaluable patients, individual data and summary statistics on percent change in IGF-1R expression will be reported. Percent of evaluable patients who achieved IGF-1R reduction will be reported. The treatment effect on IGF-1R expression.Will be analyzed using either parametric or non parametric statistical methods, depending on the normality of the distribution. |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
experimental medicine study of the pharmacodynamic effects of R1507 on breast cancer tumor cells |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the study is defined as last patient last observation |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |