Open-label study of bevacizumab (Avastin®) plus taxane monotherapy or in combination for the first-line treatment of patients with locally recurrent or metastatic breast cancer - ATHENA

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-002529-21-FI
• Date of registration: 26/06/2006
• Prospective Registration: Yes
• Primary sponsor: F.Hoffmann-La Roche Ltd
• Public title: Open-label study of bevacizumab (Avastin®) plus taxane monotherapy or in combination for the first-line treatment of patients with locally recurrent or metastatic breast cancer - ATHENA
• Scientific title: Open-label study of bevacizumab (Avastin®) plus taxane monotherapy or in combination for the first-line treatment of patients with locally recurrent or metastatic breast cancer - ATHENA
• Date of first enrolment: 05/09/2006
• Target sample size: 2291
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002529-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Austria, Czech Republic, Estonia, Finland, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent (informed consent document to be approved by the Independent Ethics Committee [IEC]) obtained prior to any study-specific procedure

2. Age =18 years

3. Able to comply with the protocol

4. Histologically or cytologically confirmed, HER2-negative, pre- or post-menopausal women with adenocarcinoma of the breast with measurable or non-measurable LR or metastatic disease, who are candidates for chemotherapy. Locally recurrent disease must not be amenable to radiation therapy or resection with curative intent
- HER2-positive patients are eligible if they have progressed after previous trastuzumab (Herceptin®) treatment in the adjuvant setting. Concomitant use of bevacizumab and trastuzumab is not allowed

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

6. Life expectancy of =12 weeks

7. Prior adjuvant chemotherapy is allowed

8. Prior radiation therapy is allowed if:
- delivered in the adjuvant setting as a part of the treatment of early breast cancer
- delivered prior to study entry for the relief of metastatic bone pain, provided that no more than 30% of marrow-bearing bone has been irradiated (if using chemotherapy backbone which is highly myelosuppressive)

9. Adequate haematological function
- Absolute neutrophil count (ANC) =1.5 x 10[9]/L AND
- Platelet count =100 x 10[9]/L AND
- Haemoglobin =9 g/dL (may be transfused to maintain or exceed this level)

10. Adequate liver function
- Total bilirubin <1.5 x upper limit of normal (ULN) AND
- AST, ALT <2.5 x ULN in patients without liver metastases; <5 x ULN in patients with liver metastases

11. Adequate renal function
- Serum creatinine =1.25 x ULN or calculated creatinine clearance =50 mL/min AND
- Urine dipstick for proteinuria <2+. Patients discovered to have =2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =1 g of protein in 24 hours

12. International normalized ratio (INR) =1.5 and PTT =1.5 x ULN within 7 days prior to enrolment

13. If female, should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to inclusion into the study. If a serum pregnancy test is not performed within 7 days prior to the first dose of bevacizumab, a confirmatory urine test (within 7 days prior to the first dose of bevacizumab) is required

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 LR or mBC

2. Concomitant hormonal therapy for LR or metastatic disease, however previous hormonal therapy is allowed for adjuvant, LR, or mBC

3. Patients must have received no radiation therapy for the treatment of metastatic disease (apart from those who received it for the relief of metastatic bone pain and with the precautions mentioned above)

4. Evidence of CNS metastases (even if previously treated). If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases

5. Pre-existing peripheral neuropathy NCI CTC-AE Grade >2 at enrolment

6. 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

7. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion

8. Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (>325 mg/day)

9. Current or recent (within 10 days of first dose of bevacizumab) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed

10. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding

11. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg)

12. Clinically significant (i.e. active) cardiovascular disease for example CVA (=6 months before enrolment), myocardial infarction (=6 months before enrolment), unstable angina, congestive heart failure (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

13. Non-healing wound, active peptic ulcer or bone fracture

14. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment

15. Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last administration of bevacizumab.

16. Men who do not agree to use effective contraception during the study and for a period of 60 days following the last administration of bevacizumab

17. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment

18. Known hypersensitivity to bevacizumab and any of its excipients, and any of the chemotherapies

19. 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Locally recurrent or metastatic breast cancer

Intervention(s)

Trade Name: Avastin
Product Name: Avastin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizumab
CAS Number: 216974-75-3
Current Sponsor code: RO4876646
Other descriptive name: rhuMAb, VEGT, anti-VEGF
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Main Objective: The primary objective is to assess the safety profile of bevacizumab when combined with taxane monotherapy or in combination as first line treatment of patients with locally recurrent (LR) or metastatic breast cancer (mBC).

Secondary Objective: - To assess the efficacy of bevacizumab when combined with taxane monotherapy or in combination as first line treatment of patients with LR or mBC as measured by time to disease progression (TTP) and overall survival (OS).

- To assess the safety of bevacizumab in patients who develop CNS metastases during and for 6 months following the treatment period.

Primary end point(s): The incidence of SAEs related to bevacizumab and the incidence of specific AEs (serious and non-serious) such as hypertension, proteinuria, arterial and venous thromboembolism, CHF, CNS bleeding, other haemorrhages, wound-healing complications, and gastrointestinal perforations, are considered as primary endpoints. Patients with ECOG PS 2 will be analyzed separately.

Secondary ID(s)

MO19391