Metronomic Therapy in Metastatic Breast Cancer.

NCT01131195 | Completed Phase 3

• 4 other identifiers: SAKK 24/09SWS-SAKK-24-09EU-21025CDR0000669252
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 23

Brief Summary

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.

Conditions

Breast Cancer

Keywords

HER2-negative breast cancer; recurrent breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 3-5 adverse events

  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.

  Documentation of AE observed during trial treatment and in follow-up until resolution

Secondary Outcomes (5)

• Objective response (OR)

  the best response under trial treatment

• Disease control (DC)

  best response under trial treatment at 24 weeks after randomization

• Progression-free survival (PFS)

  from randomization until documented tumor progression

• Overall survival (OS)

  the time from randomization to death from any cause

• Time to specific grade 3-5 adverse events

  Time from randomization until the first occurrence of the predefined grade 3-5 adverse events for the primary endpoint.

Study Arms (2)

Arm A: bevacizumab and paclitaxel

ACTIVE COMPARATOR

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

Arm B: bevacizumab, cyclophosphamide and capecitabine

ACTIVE COMPARATOR

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

Interventions

bevacizumab, Paclitaxel BIOLOGICAL

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.

Also known as: Avastin

Arm A: bevacizumab and paclitaxel

Bevacizumab, Cyclophosphamide, Capecitabine BIOLOGICAL

Bevacizumab (10 mg/kg) i.v. is given every two weeks. Cyclophosphamide (50 mg) and capecitabine (3x 500 mg) p.o. are given daily

Also known as: Avastin, Xeloda

Arm B: bevacizumab, cyclophosphamide and capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (23)

Hirslanden Klinik Aarau

Aarau, CH-5001, Switzerland

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

RSV-GNW Spitalzentrum Oberwallis

Brig, 3900, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Kantonsspital Frauenfeld

Frauenfeld, 8501, Switzerland

Location

Kantonsspital Freiburg

Fribourg, 1708, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Luzern

Luzerne, CH-6000, Switzerland

Location

Oncology Institute of Southern Switzerland - IOSI Ticino

Mendrisio, CH-6850, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Hopital Regional de Sion-Herens-Conthey

Sion, CH -1951, Switzerland

Location

Regionalspital Thun

Thun, 3600, Switzerland

Location

Spital Uster

Uster, 8610, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Onkozentrum - Klinik im Park

Zurich, 8002, Switzerland

Location

Onkozentrum Hirslanden

Zurich, CH-8008, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (2)

• Rochlitz C, Bigler M, von Moos R, Bernhard J, Matter-Walstra K, Wicki A, Zaman K, Anchisi S, Kung M, Na KJ, Bartschi D, Borner M, Rordorf T, Rauch D, Muller 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. doi: 10.1186/s12885-016-2823-y.

  PMID: 27724870 RESULT

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

  PMID: 34037241 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Paclitaxel; Cyclophosphamide; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Christoph Rochlitz, MD

  Universitaetsspital-Basel

  STUDY CHAIR

• Ralph Winterhalder, MD

  Luzerner Kantonsspital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 26, 2010
• Study Start: July 19, 2010
• Primary Completion: December 14, 2012
• Study Completion: February 28, 2018
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (23)