Effect of angiogenesis inhibiting therapy in patients progressing on endocrine treatment and patients with triple negative breast cancer - a translational phase II study within theSwedish Association of Breast Oncologists SABO-2010-01

• Conditions: Patients with breast cancer who are oestrogen receptor positive but HER2 negative and progressing on endocrine therapy. Patients with locally advanced or recurrent triple negative breast cancer (TNBC) can also be included. Patients with TNBC will not receive endocrine therapy.; MedDRA version: 14.1Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-022065-10-SE
• Lead Sponsor: Sahlgrenska University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-25
• Last Update Posted: 10 March 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

1.Written informed consent approved by the Independent Ethical Board.
2.Female patients >18 years with breast cancer confirmed by histology.
3. Relapse (local or distant) and progress on 1st, 2nd or 3rd line endocrine therapy.
4.Measurable or evaluable disease. Locally advanced or metastatic TNBC
5. ECOG PS 0-2
6.Life expectancy of >3 months

6.Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders.
Haematologic function
Absolute neutrophil count (ANC) = 1.5 x 109/L and
Platelet count = 100 x 109/L and
Haemoglobin = 9g /dL (transfusion allowed to reach this level)
Liver function
Total bilirubin <1.5 x upper limit of normal (ULN) and
AST, ALT <2.5 x ULN (patients without liver metastases)
AST, ALT <5 x ULN (patients with liver metastases)
Renal function
Serum creatinine = 1.25 x ULN or calculated creatinine clearance = 50 mL/min and
Urine dipstick for proteinuria < 2+. Patients with = 2+ proteinuria on dipstick analysis at baseline should undergo a 24 hour urine collection resulting in = 1g of protein in 24 hours.
International normalised ratio (INR) = 1.5 and PTT = 1.5 x UNL within 7 days prior to enrolment.
7.ECOG performance status 0-2.
8.Patients in child-bearing age must have adequate contraception.
9.Tumour and blood samples according to APPENDIX II available.

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. Previous chemotherapy for recurrent breast cancer (local or distant metastasis).
2. Symptoms of CNS metastases. If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases.
3. Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment.
4. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion.
5. Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (>325 mg/day).
6. History or evidence of inherited bleeding diathesis or coagulapathy with the risk of bleeding.
7. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg).
8. Clinically significant (i.e. active) cardiovascular disease for example CVA (=6 months before enrolment), myocardial infarction (MI) (=6 months before enrolment), unstable angina, CHF NYHA Class =II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication.
9. Non-healing wound, active peptic ulcer or bone fracture.
10. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment.
11. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
12. Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: 1. To evaluate the effect of additional angiogenesis inhibiting therapy to endocrine treatment in patients with an endocrine resistant breast cancer.<br>2. To discover new potential predictive markers for this regimen in metastatic breast cancer.<br>3. To discover potential markers for monitoring treatment effect. <br>;Secondary Objective: Secondary endpoints:<br>• Progression-free survival (PFS)<br>• Identification of treatment predictive markers and markers for monitoring therapy effect by evaluation of molecular characteristics before start of therapy and modifications during treatment. <br>• Tolerance and safety assessment.<br>• Overall survival<br>;Primary end point(s): • Overall response rates (ORR); complete response (CR) and partial response (PR) by conventional radiological procedures <br>• Clinical benefit (CR, PR and stable disease >24 weeks)<br>