Biweekly Avastin and Docetaxel as the First Line Treatment for Patients With Metastatic Breast Cancer (AINO)

Single Arm Study of the Combination of Biweekly Avastin and Docetaxel as the First Line Treatment for Patients With Metastatic Breast Cancer

The purpose of this study is to evaluate the efficacy and safety of the combination of biweekly docetaxel and bevacizumab in the first line treatment of metastatic breast cancer by using Response Evaluation Criteria In Solid Tumors (RECIST criteria) and NCI Common Terminology Criteria for Adverse Events (NCI CTC-AE) version 3. In addition several biochemical makers are tested as possible predictive factors.

Study Overview

• Status: Terminated
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Docetaxel

Detailed Description

Patients with histologically or cytologically proven measurable or nonmeasurable metastatic breast cancer are treated with a combination of biweekly docetaxel and bevacizumab as the first line treatment in multicenter phase II trial. The outcome measures would be PFS, Response rate (RECIST), duration of response, safety (NCI CTC-AE version 3) and survival. In addition several biochemical makers are tested as possible predictive factors. Treatment would be continued until PD, patient's refusal or treatment discontinuation due to side-effects or patients death. In responding patients bevacizumab would be continued either alone or in hormone receptor positive patients combined with hormone treatment until progression.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Tampere, Finland
    • Tampere Unviersity Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• written informed concent
• age > or equal 18 years
• able to comply with the protocol
• histologically or cytologically confirmed, Her-2 negative, adenocarcinoma of the breast with measurable or nonmeasurable metastatic disease, chemotherapy indicated
• ECOG 0-2, life expectancy of over or qual to 12 wks
• prior neo/adjuvant chemotherapy allowed
• prior adjuvant taxane therapy is allowed, DFS> or equal 6 months
• previous hormonal therapy allowed
• prior RT is allowed as adjuvant setting or to relief of metastatic bone pain, no more than 30% of marrow-bearing bone irradiated
• Adequate haematological function
• adequate liver function total bilirubin <1.5 x upper limit of normal and AST,ALT <2.5 x ULN in patients without liver metastases; <5 x ULN in patients with liver metastases
• adequate renal function serum creatinine <or equal 1,5x ULN or calculated creatinine clearance > or equal 50mL/min and urine dipstick for proteinuria <2+. Patients discovered to have or equal proteinuria or dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate < or equal 1 g of protein in 24 hours
• INR<or equal 1.5 and PTT< or equal 1.5 x ULN within 7 days prior to enrolment. Anticoagulation treatment not allowed
• if female, should not be pregnant or breast-feeding. Women with an intact uterus must have a negative serum pregnancy test within 28 days prior to inclusion into the study

Exclusion Criteria:

• previous chemotherapy for mBC
• radiation therapy for the treatment of metastatic disease within 28 days
• evidence of CNS metastases. If symptomatic, the patient should be scanned within 28 days to enrolment to rule out CNS metastases
• pre-existing peripheral neuropathy NCI CTC-AE grade > 2 at enrolment
• major surgery, significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment
• Minor surgery, including insertion off an indwelling catheter, within 24 hours prior to the first line bevacizumab infusion
• Current or recent(within 10 daÿs of first dose of bevacizumab) use of aspirin (>325mg/day)
• current or recent (within 10 days of first dose of bevacizumab) use of oral or parenteral anticoagulants or thrombolytic agents.
• history of evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
• uncontrolled hypertension (systolic >150mmHg and/or diastolic>100mmHg)
• Clinically significant cardiovascular disease for example CVA, myocardial infarction, unstable angina, congestive heart failure NYHA Class > or equal II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication
• non- healing wound, active peptic ulcer or bone fracture
• history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment
• past of current history (within the last 5 years) of other malignancies except curatively treated basal and squamous cell carcinoma of the skin or in-situ carcinoma of the cervix
• treatment with any other investigational agent, or participation in another clinical drug trial within 28 days prior to enrolment
• evidence of any other disease, neurological, psychiatric 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
• history of thrombotic disorders within last six months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chemoterapy; docetaxel/paclitaxel + bevacizumab	Drug: Docetaxel; Other Names: bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	increase of cancer burden	1-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy, changes in metastacic lesions	response rate	every 2 months
overall survival	alive	2- 3 months
time to response	decrease of cancer burden	2 months
duration of response	gain	2 months
progression free survival from first relapse	second increase of cancer burden	2 months
safety, occurence of side-effects	side effects according to NCICTC-AE version 3.0	1 month

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Collaborators: Turku University Hospital; Oulu University Hospital
• Investigators: Principal Investigator: Pirkko-Liisa I Kellokumpu-Lehtinen, MD, Tampere University Hospital

Publications and helpful links

General Publications

• Tiainen L, Korhonen EA, Leppanen VM, Luukkaala T, Hamalainen M, Tanner M, Lahdenpera O, Vihinen P, Jukkola A, Karihtala P, Aho S, Moilanen E, Alitalo K, Kellokumpu-Lehtinen PL. High baseline Tie1 level predicts poor survival in metastatic breast cancer. BMC Cancer. 2019 Jul 24;19(1):732. doi: 10.1186/s12885-019-5959-8.
• Tiainen L, Tanner M, Lahdenpera O, Vihinen P, Jukkola A, Karihtala P, Paunu N, Huttunen T, Kellokumpu-Lehtinen PL. Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer. Anticancer Res. 2016 Dec;36(12):6431-6438. doi: 10.21873/anticanres.11241.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2009
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: December 19, 2008
• First Submitted That Met QC Criteria: September 17, 2009
• First Posted (Estimate): September 18, 2009

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 27, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: breast cancer; chemotherapy; bevacizumab; metastatic; Phase II; docetaxel; first line chemotherapy; metastatic breast cancer patients
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: EudraCT 2008-003527-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Clinical Study Report