Bevacizumab and Paclitaxel or Bevacizumab, Cyclophosphamide, and Capecitabine as First-Line Therapy in Treating Women With Locally Advanced, Recurrent, or Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01131195
First received: May 25, 2010
Last updated: December 8, 2013
Last verified: December 2013
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, cyclophosphamide, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether bevacizumab is more effective when given together with paclitaxel or cyclophosphamide and capecitabine in treating patients with breast cancer.

PURPOSE: This randomized phase III trial is studying the side effects of giving bevacizumab together with paclitaxel and to see how well it works compared with giving bevacizumab together with cyclophosphamide and capecitabine as first-line therapy in treating women with locally advanced, recurrent, or metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: bevacizumab, Paclitaxel
Biological: Bevacizumab, Cyclophosphamide, Capecitabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Tolerability of Bevacizumab Plus Paclitaxel vs. Bevacizumab Plus Metronomic Cyclophosphamide and Capecitabine as First-Line Therapy in Patients With HER2-Negative Metastatic or Locally Recurrent Breast Cancer - A Multicenter, Randomized Phase III Trial

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Incidence of grade 3-5 adverse events [ Time Frame: Documentation of AE observed during trial treatment and in follow-up until resolution ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response [ Time Frame: the best response under trial treatment ] [ Designated as safety issue: No ]
  • Disease control [ Time Frame: best response under trial treatment ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: from randomization until documented tumor progression ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: the time from randomization to death from any cause ] [ Designated as safety issue: No ]
  • Time to specific grade 3-5 adverse events [ Time Frame: Time from randomization until the first occurrence of the predefined grade 3-5 adverse events for the primary endpoint. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 142
Study Start Date: June 2010
Estimated Study Completion Date: October 2015
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A: bevacizumab and paclitaxel
Bevacizumab (10 mg/kg) i.v. is given every two weeks. Paclitaxel (90 mg/m2) i.v. is given on days 1, 8, and 15 of a 4 week cycle. Both medications are given until PD, unacceptable adverse event, or consent withdrawal. If an unacceptable adverse event to any of the drugs in this treatment arm occurs the remaining tolerated drug is given until PD, consent withdrawal, or unacceptable adverse event according to local investigators opinion.
Biological: bevacizumab, Paclitaxel
Bevacizumab (10 mg/kg) i.v. is given every two weeks. Paclitaxel (90 mg/m2) i.v. is given on days 1, 8, and 15 of a 4 week cycle.
Other Name: Avastin
Active Comparator: Arm B: bevacizumab, cyclophosphamide and capecitabine
Bevacizumab (10 mg/kg) i.v. is given every two weeks. Cyclophosphamide (50 mg) and capecitabine (3x 500 mg) p.o. are given daily. All three medications are given until PD, unacceptable adverse event, or consent withdrawal. If an unacceptable adverse event to any of the drugs in this treatment arm occurs the remaining tolerated drug(s) is (are) given until PD, consent withdrawal, or unacceptable adverse event according to local investigators opinion
Biological: Bevacizumab, Cyclophosphamide, Capecitabine
Bevacizumab (10 mg/kg) i.v. is given every two weeks. Cyclophosphamide (50 mg) and capecitabine (3x 500 mg) p.o. are given daily
Other Names:
  • Avastin
  • Xeloda

Detailed Description:

OBJECTIVES:

  • To determine if bevacizumab and paclitaxel versus bevacizumab, metronomic cyclophosphamide, and capecitabine as first-line therapy causes less medication-related adverse events in women with HER2-negative metastatic, locally advanced, or recurrent breast cancer.
  • To compare quality of life (QOL) in patients treated with these regimens.
  • To replicate previous findings of better QOL in patients with complete response or partial response versus stable disease for 6 months or greater.
  • To determine the predictive value of baseline QOL for the duration of a meaningful change in QOL of patients treated with chemotherapy.
  • To determine the associations between the QOL endpoints, selected health economics, and clinical endpoints.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor response (measurable vs evaluable disease), WHO performance status (0 or 1 vs 2), and center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and paclitaxel IV on days 1, 8, and 15. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral cyclophosphamide once daily on days 1-28, and oral capecitabine 3 times a day on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaire (BL-QA) and health economics questionnaires (BL-HEA and EQ-5D) at baseline, during, and after completion of study therapy.

After completion of study treatment, patients are followed up at 1 month, every 3 months for 1 year, and then every 6 months for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the breast

    • Locally advanced, recurrent, or metastatic disease
  • HER2-negative disease
  • Measurable or evaluable disease
  • Candidate for taxane-based chemotherapy
  • No presence or history of CNS metastasis

    • Clinical suspicion of CNS metastasis must be confirmed by CT or MRI scan
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • WHO performance status 0-2
  • Neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin ≥ 80 g/L
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in case of liver metastases or ≤ 10 times ULN in case of bone metastases)
  • Serum creatinine ≤ 1.5 times ULN
  • Urine protein < 2+ by dipstick OR ≤ 1 g by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study therapy
  • Patients with INR > 1.5 (or Quick ≤ 70%) OR aPTT > 1.5 times ULN within 7 days prior to expected first trial treatment must be receiving anticoagulant medication

    • Patients receiving full-dose oral or parental anticoagulants may be included in the trial provided anticoagulant dosing has been stable for at least 2 weeks prior to trial entry and the appropriate coagulation monitoring tests are within local therapeutic limits
  • Must be compliant and geographically proximal for staging and follow-up
  • No previous malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
  • No known hypersensitivity to trial drugs or its active compound (e.g., fluoropyrimidine), any other components of the trial drugs, or drugs formulated with cremophor EL including hypersensitivity to Chinese hamster ovary cell products or any other humanized recombinant antibodies
  • No preexisting peripheral motor or sensory neuropathy > NCI CTCAE grade 2 (i.e., moderate symptoms or limiting instrumental activities of daily living)
  • No history or evidence of inherited bleeding diathesis, coagulopathy with the risk of bleeding, serious nonhealing wound, active peptic ulcer, nonhealing bone fracture, or bleeding metastases
  • No history of abdominal fistula, grade 4 bowel obstruction, or gastrointestinal perforation or intra-abdominal abscess within the past 6 months
  • No evidence of other medical conditions that would impair the ability of the patient to participate in the trial or might preclude therapy with trial drugs, including any of the following:

    • DPD deficiency
    • Severe respiratory, cardiac, hepatic, or renal disease
    • Active infection
    • Uncontrolled diabetes mellitus
    • Uncontrolled hypertension ≥ 140/100 mm Hg
    • Myocardial infarction within the past 12 months
    • Cerebrovascular accident or stroke within the past 6 months
    • History of hemorrhagic disorders
  • No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, filling out quality-of-life forms, or interfering with compliance for oral drug intake

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy for metastatic or locally recurrent breast cancer
  • No prior radiotherapy for metastatic disease

    • Prior radiotherapy for the relief of metastatic bone pain allowed provided no more than 30% of marrow-bearing bone was irradiated
  • At least 12 months since prior bevacizumab or other anti-VEGF therapy
  • At least 12 months since prior capecitabine, continuous (> 24 hours) fluorouracil infusion, or other oral fluoropyrimidine (e.g., eniluracil/fluorouracil, uracil/tegafur, S1, or emitefur)
  • At least 12 months since prior taxane-based chemotherapy
  • At least 6 months since other prior (neo)adjuvant chemotherapy
  • At least 30 days since prior treatment in another clinical trial
  • At least 24 hours since prior minor surgical procedures
  • At least 28 days since prior and no concurrent major surgical procedures (including open biopsy) and no anticipation of the need for major surgery during the first course of this trial
  • At least 10 days since prior hormone therapy for metastatic disease
  • No continuous daily treatment with corticosteroid except for inhaled steroids
  • No concurrent chronic daily aspirin > 325 mg/day
  • No concurrent chronic daily clopidogrel > 75 mg/day
  • No other concurrent anticancer treatments
  • No other concurrent investigational treatments or experimental drugs
  • No other concurrent drug therapy contraindicated for use with the trial drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01131195

Locations
Switzerland
Hirslanden Klinik Aarau
Aarau, Switzerland, CH-5001
Kantonspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Spitalzentrum Biel
Biel, Switzerland, CH-2501
RSV-GNW Spitalzentrum Oberwallis
Brig, Switzerland, 3900
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Kantonsspital Frauenfeld
Frauenfeld, Switzerland, 8501
Kantonsspital Freiburg
Freiburg, Switzerland, 1708
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Luzern
Luzerne, Switzerland, CH-6000
Oncology Institute of Southern Switzerland - IOSI Ticino
Mendrisio, Switzerland, CH-6850
Kantonsspital Olten
Olten, Switzerland, CH-4600
Hopital Regional de Sion-Herens-Conthey
Sion, Switzerland, CH -1951
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Regionalspital Thun
Thun, Switzerland, 3600
Spital Uster
Uster, Switzerland, 8610
Kantonsspital Winterthur
Winterthur, Switzerland, 8401
Onkozentrum Hirslanden
Zurich, Switzerland, CH-8008
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
City Hospital Triemli
Zurich, Switzerland, CH-8063
Onkozentrum - Klinik im Park
Zurich, Switzerland, 8002
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Christoph Rochlitz, MD Universitaetsspital-Basel
Study Chair: Ralph Winterhalder, MD Luzerner Kantonsspital
  More Information

Additional Information:
No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01131195     History of Changes
Other Study ID Numbers: SAKK 24/09, SWS-SAKK-24-09, EU-21025, CDR0000669252
Study First Received: May 25, 2010
Last Updated: December 8, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
HER2-negative breast cancer
recurrent breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Capecitabine
Cyclophosphamide
Paclitaxel
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 18, 2014