Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Nonmetastatic Breast Cancer

NCT01093235 | Unknown Phase 3

• 6 other identifiers: CDR0000668530CRCA-CCTC-WCTU-ARTemisISRCTN68502941EUDRACT-2008-002322-11EU-21017MREC-08/H1102/104
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, fluorouracil, epirubicin hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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. It is not yet known whether giving combination chemotherapy together with or without bevacizumab is more effective in treating patients with nonmetastatic breast cancer. PURPOSE: This randomized phase III trial is studying how well giving combination chemotherapy works compared with giving combination chemotherapy together with bevacizumab in treating patients with nonmetastatic breast cancer.

Conditions

Breast Cancer; Cardiac Toxicity; Perioperative/Postoperative Complications

Keywords

cardiac toxicity; perioperative/postoperative complications; HER2-negative breast cancer; male breast cancer; estrogen receptor-negative breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-negative breast cancer; progesterone receptor-positive breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; inflammatory breast cancer

Outcome Measures

Primary Outcomes (1)

• Complete pathological response rates (tumor and lymph nodes)

Secondary Outcomes (7)

• Disease-free survival

• Overall survival

• Pathological complete response rate in breast alone

• Radiological response after 3 and 6 courses of chemotherapy

• Rate of breast conservation

Interventions

bevacizumab BIOLOGICAL

cyclophosphamide DRUG

docetaxel DRUG

epirubicin hydrochloride DRUG

fluorouracil DRUG

assessment of therapy complications PROCEDURE

neoadjuvant therapy PROCEDURE

quality-of-life assessment PROCEDURE

therapeutic conventional surgery PROCEDURE

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed invasive breast cancer * HER2-negative disease * IHC 0/1 OR IHC 2+ and FISH negative * Must meet 1 of the following criteria: * Unifocal tumor meeting 1 of the following criteria: * T2 or T3 tumors (radiological size \> 20 mm) * T4 tumor of any size with direct extension to the chest wall or the skin * Inflammatory carcinoma with tumor of any size * Multifocal tumor meeting the following criteria: * The sum of each tumors' maximum diameter must be ≥ 20 mm (total radiological tumor size ≥ 20 mm) * Other locally advanced disease meeting 1 of the following criteria: * Any T stage with involvement of large or fixed axillary lymph nodes (radiological diameter \> 20 mm or clinical N2) and primary breast tumor of any diameter * Any T stage with involvement of large or fixed axillary lymph nodes (radiological diameter \> 20 mm or clinical N2), without a primary breast tumor identified and the presence of breast cancer in a lymph node must be histopathologically confirmed by lymph node biopsy (tru-cut or whole lymph node) * Embedded paraffin tumor block available from pre-chemotherapy biopsy and surgical specimen * Bilateral disease allowed * No evidence of metastatic disease * No prior breast cancer except for ductal carcinoma in situ of the breast surgically cured \> 10 years ago * Any hormone receptor status PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * WBC \> 3 x 10\^9/L * Hemoglobin \> 10 g/dL * Platelet count \> 100 x 10\^9/L * AST/ALT ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2 times ULN * Bilirubin normal * Isolated elevation of bilirubin to ≤ 3 times ULN with a presumptive diagnosis of Gilbert syndrome allowed if AST/ALT and alkaline phosphatase are within normal limits * Creatinine ≤ 1.5 times ULN * PT and PTT/aPTT ≤ 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * Must be fit to receive chemotherapy on this trial, in the opinion of the responsible clinician, as indicated by the following criteria: * No clinically significant cardiac abnormalities * No myocardial infarction within the past 6 months * LVEF normal (at least 50%) by MUGA scan or echocardiogram * No prior ischemic heart disease, cerebrovascular disease, peripheral vascular disease, arterial or venous thromboembolic disease, cardiac failure, inflammatory bowel disease, gastroduodenal ulcer, symptomatic diverticulitis, or bleeding diathesis * No uncontrolled hypertension (systolic BP \> 150 mm Hg or diastolic BP \> 90 mm Hg) with or without antihypertensive medication * Patients with initial blood pressure elevations are eligible provided initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria * No other previous malignancy except basal cell carcinoma, carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast treated by surgery only and disease-free for 10 years * No concurrent medical or psychiatric problem that might prevent completion of treatment or follow-up * No presence of active uncontrolled infection * No history of nephritic or nephrotic syndrome * No traumatic injury within the past 28 days * No evidence of other disease that, in the opinion of the investigator, places the patient at high risk of treatment-related complications * No nonhealing wound, peptic ulcer, or bone fracture PRIOR CONCURRENT THERAPY: * No prior neoadjuvant endocrine therapy * No prior chemotherapy or radiotherapy * No major surgical procedure within the past 28 days * No concurrent full therapeutic dose of anticoagulants or aspirin \> 325 mg/day, clopidogrel \> 75 mg/day, or corticosteroids

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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

RECRUITING

Related Publications (3)

• Ali HR, Dariush A, Thomas J, Provenzano E, Dunn J, Hiller L, Vallier AL, Abraham J, Piper T, Bartlett JMS, Cameron DA, Hayward L, Brenton JD, Pharoah PDP, Irwin MJ, Walton NA, Earl HM, Caldas C. Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial. Ann Oncol. 2017 Aug 1;28(8):1832-1835. doi: 10.1093/annonc/mdx266.

  PMID: 28525534 DERIVED

• Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Gounaris I, Abraham JE, Hughes-Davies L, McAdam K, Chan S, Ahmad R, Hickish T, Rea D, Caldas C, Bartlett JMS, Cameron DA, Provenzano E, Thomas J, Hayward RL; ARTemis Investigators Group. Disease-free and overall survival at 3.5 years for neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide, for women with HER2 negative early breast cancer: ARTemis Trial. Ann Oncol. 2017 Aug 1;28(8):1817-1824. doi: 10.1093/annonc/mdx173.

  PMID: 28459938 DERIVED

• Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. doi: 10.1016/S1470-2045(15)70137-3. Epub 2015 May 11.

  PMID: 25975632 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity; Postoperative Complications; Breast Neoplasms, Male; Inflammatory Breast Neoplasms

Interventions

Bevacizumab; Cyclophosphamide; Docetaxel; Epirubicin; Fluorouracil; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics

Study Officials

• Helena Earl, MBBS, PhD, FRCP

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 25, 2010
• Study Start: April 1, 2009
• Primary Completion: April 1, 2012
• Last Updated: March 25, 2010

Record last verified: 2010-03

Locations

GB (1)