An exploratory study to evaluate the biological activity of R1507, a human monoclonal antibody, antagonist of the insulin-like growth factor receptor (IGF-1R) in women with operable breast cancer

• Conditions: Female patients with operable breast cancer, fulfilling the following criteria.; MedDRA version: 9.1Level: LLTClassification code 10006204Term: Breast carcinoma

• Registration Number: EUCTR2008-004128-22-GB
• Lead Sponsor: F.Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-17
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 70

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

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. 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: First Study Part:<br>To evaluate the effect of R1507 treatment on IGF-1R expression in breast cancer cells.<br>Second Study Part:<br>To define and confirm a PK/PD threshold effect of R1507 by assessing lower dose levels<br>;Secondary Objective: • To evaluate the effect of R1507 treatment in breast cancer cells:<br>on p-AKT level<br>on Ki67 index <br>on apoptotic index <br>•To correlate R1507 PK parameters in serum with biologic changes in tumor tissue<br>•To evaluate the safety and tolerability of R1507 in patients with breast cancer <br>;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. <br>The treatment effect on IGF-1R expression.Will be analyzed using either parametric or non parametric statistical methods, depending on the normality of the<br>distribution.