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Metronomic Therapy in 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: May 2, 2017
Last verified: May 2017
May 25, 2010
May 2, 2017
July 19, 2010
December 14, 2012   (Final data collection date for primary outcome measure)
Incidence of grade 3-5 adverse events [ Time Frame: Documentation of AE observed during trial treatment and in follow-up until resolution ]
Patients who have experienced at least one of the adverse event grade ≥ 3 according to the NCI CTCAE criteria 4.0 are considered for the primary endpoint.
Incidence of grade 3-5 adverse events
Complete list of historical versions of study NCT01131195 on ClinicalTrials.gov Archive Site
  • Objective response (OR) [ Time Frame: the best response under trial treatment ]
    OR is the best response under trial treatment, defined as a complete response (CR) or partial response (PR) as assessed by RECIST v1.1.
  • Disease control (DC) [ Time Frame: best response under trial treatment at 24 weeks after randomization ]
    DC is the best response under trial treatment, defined as CR + PR + stable disease.
  • Progression-free survival (PFS) [ Time Frame: from randomization until documented tumor progression ]
    PFS is calculated from randomization until documented tumor progression according to RECIST 1.1 or death of any cause, whichever occurs first.
  • Overall survival (OS) [ Time Frame: the time from randomization to death from any cause ]
    OS is defined as the time from randomization to death from any cause
  • 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. ]
    Time from randomization until the first occurrence of the predefined grade 3-5 adverse events for the primary endpoint.
  • Objective response
  • Disease control
  • Progression-free survival
  • Overall survival
  • Time to specific grade 3-5 adverse events
  • Any adverse event (hematological adverse events of 2 or less are excluded)
  • Patients who have experienced at least one adverse event of grade 3 or greater
  • Any delay and/or dose reduction
  • Quality of life
Not Provided
Not Provided
 
Metronomic Therapy in Metastatic Breast Cancer.
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.

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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Breast Cancer
  • 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
  • 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
  • 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.
    Intervention: Biological: bevacizumab, Paclitaxel
  • 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
    Intervention: Biological: Bevacizumab, Cyclophosphamide, Capecitabine
Rochlitz C, Bigler M, von Moos R, Bernhard J, Matter-Walstra K, Wicki A, Zaman K, Anchisi S, Küng M, Na KJ, Bärtschi D, Borner M, Rordorf T, Rauch D, Müller A, Ruhstaller T, Vetter M, Trojan A, Hasler-Strub U, Cathomas R, Winterhalder R; Swiss Group for Clinical Cancer Research (SAKK). SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial. BMC Cancer. 2016 Oct 10;16(1):780.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
142
June 30, 2019
December 14, 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
 
NCT01131195
SAKK 24/09
SWS-SAKK-24-09
EU-21025
CDR0000669252
No
Not Provided
No
Not Provided
Swiss Group for Clinical Cancer Research
Swiss Group for Clinical Cancer Research
Not Provided
Study Chair: Christoph Rochlitz, MD Universitaetsspital-Basel
Study Chair: Ralph Winterhalder, MD Luzerner Kantonsspital
Swiss Group for Clinical Cancer Research
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP