Combination Chemotherapy With or Without Capecitabine and/or Trastuzumab Before Surgery in Treating Women With Stage I, Stage II, or Stage III Breast Cancer

NCT00288002 | Completed Phase 3

• 7 other identifiers: CDR0000455125GBG-GEPARQUATTROGBG-40EU-205101AVENTIS-GBG-GEPARQUATTROROCHE-AVENTIS-GBG-GEPARQUATTROEUDRACT-2005-001546-17
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as epirubicin, cyclophosphamide, docetaxel, and capecitabine, 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 trastuzumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy together with monoclonal antibodies before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving monoclonal antibodies after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without capecitabine and/or trastuzumab in treating breast cancer. PURPOSE: This randomized phase III trial is studying epirubicin, cyclophosphamide, and docetaxel to compare how well they work with or without capecitabine and/or trastuzumab before surgery in treating women with stage I, stage II, or stage III breast cancer.

Conditions

Breast Cancer

Keywords

inflammatory breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IA breast cancer; stage IB breast cancer; estrogen receptor-negative breast cancer; estrogen receptor-positive breast cancer; HER2-negative breast cancer; HER2-positive breast cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response

Interventions

trastuzumab BIOLOGICAL

capecitabine DRUG

cyclophosphamide DRUG

docetaxel DRUG

epirubicin hydrochloride DRUG

adjuvant therapy PROCEDURE

conventional surgery PROCEDURE

neoadjuvant therapy PROCEDURE

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed unilateral or bilateral primary breast cancer * Meets 1 of the following staging criteria: * Clinical stage T4 or T3 disease * Clinical stage T1 and pathologic stage N+ by sentinel lymph node biopsy OR clinical stage T2, N+ disease AND estrogen receptor (ER) or progesterone receptor (PR) positive tumor * ER and PR negative tumor (T1-4, N0-3, M0) * Disease confirmed by core biopsy * No fine-needle aspiration or incisional biopsy * Bidimensionally measurable disease\* * Tumor lesion palpable and measures ≥ 2 cm OR tumor lesion ≥ 1 cm in maximum diameter by sonography * For inflammatory disease, extent of inflammation can be used as measurable lesion NOTE: \*In patients with multifocal or multicentric breast cancer, the largest lesion should be measured * Candidate for adjuvant chemotherapy * No low- or moderate-risk patients who are doubtful candidates for adjuvant chemotherapy and do not fulfill the staging criteria * Known HER-2/neu status by core biopsy * HER-2/neu positive tumor is defined as +3 by immunohistochemistry \[IHC\] OR positive by fluorescence in situ hybridization (FISH) * No evidence of distant metastasis * Hormone receptor status: * ER- or PR-positive tumor OR ER- and PR-negative tumor PATIENT CHARACTERISTICS: * No male patients * Menopausal status not specified * Karnofsky performance status 80-100% * Life expectancy ≥ 10 years (disregarding diagnosis of cancer) * Normal cardiac function confirmed by ECG * LVEF ≥ 55% by cardiac ultrasound * Neutrophil count ≥ 2,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL * Bilirubin normal * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Alkaline phosphatase (AP) ≤ 5 times ULN OR * AP ≤ 2.5 times ULN AND AST and/or ALT ≤ 1.5 times ULN * Creatinine ≤ 2 mg/dL * Creatinine clearance ≥ 50 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective nonhormonal contraception * No motor or sensory neuropathy ≥ grade 2 * No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer * No New York Heart Association class II-IV congestive heart failure * No coronary artery disease * No history of myocardial infarction * No uncontrolled arterial hypertension (i.e., blood pressure ≥ 160/90 mm Hg despite antihypertensive therapy) * No rhythm abnormalities requiring permanent therapy * No history of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures that would preclude giving informed consent * No active infection * No active peptic ulcer * No unstable diabetes mellitus or insulin-dependent type II diabetes mellitus * No other serious illness or medical condition * No known hypersensitivity reaction to investigational compounds or incorporated substances * No definite contraindications for the use of corticosteroids * No known dihydropyrimidine dehydrogenase deficiency * Must be fit for anthracycline/taxane-containing chemotherapy PRIOR CONCURRENT THERAPY: * No prior chemotherapy for any malignancy * No prior radiation therapy for breast cancer * No concurrent bisphosphonates during chemotherapy * Bisphosphonates allowed postoperatively * No chronic treatment with corticosteroids unless it is initiated \> 6 months prior to study entry and is given at low doses (≤ 20 mg methylprednisolone or equivalent) * No concurrent amifostine during chemotherapy * No concurrent cardioprotectors (e.g., dexrazoxane) during chemotherapy * No concurrent sex hormone therapy * No concurrent virostatic agents (e.g., sorivudine or brivudine) * No concurrent aminoglycosides * No other concurrent experimental drugs or anticancer therapy * At least 30 days since prior participation in another clinical trial with any investigational (not marketed) drug

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

Sponsors & Collaborators

• GBG Forschungs GmbH: lead

Study Sites (1)

Universitaetsfrauenklinik Frankfurt

Neu-Isenburg, D-63263, Germany

Location

Related Publications (7)

• Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kuhn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, von Minckwitz G. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2024-31. doi: 10.1200/JCO.2009.23.8451. Epub 2010 Mar 22.

  PMID: 20308670 RESULT

• von Minckwitz G, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kuhn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, Untch M. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2015-23. doi: 10.1200/JCO.2009.23.8303. Epub 2010 Mar 22.

  PMID: 20308671 RESULT

• Witzel I, Loibl S, von Minckwitz G, Mundhenke C, Huober J, Hanusch C, Henschen S, Hauschild M, Lantzsch T, Tesch H, Latos K, Just M, Hilfrich J, Barinoff J, Eulenburg CZ, Roller M, Untch M, Muller V. Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial. Breast Cancer Res Treat. 2010 Sep;123(2):437-45. doi: 10.1007/s10549-010-1030-9. Epub 2010 Jul 10.

  PMID: 20623180 RESULT

• Riethdorf S, Loibl S, Komor M, et al.: Incidence and kinetics of circulating tumor cells in breast cancer patients treated with primary systemic therapy including trastuzumab for patients with HER2-positive tumors a translational project within the study GeparQuattro. [Abstract] Breast Cancer Res Treat 106 (1): A-5025, S214, 2007.

  RESULT

• von Minckwitz G, Rezai M, Loibl S, et al.: Evaluating the efficacy of capecitabine given concomitantly or in sequence to epirubicin/cyclophosphamide docetaxel as neoadjuvant treatment for primary breast cancer. First efficacy analysis of the GBG/AGO intergroup-study GeparQuattro. [Abstract] Breast Cancer Res Treat 106 (1): A-79, S21-2, 2007.

  RESULT

• von Minckwitz G, Rezai M, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Blohmer JU, Costa SD, Jackisch C, Paepke S, Schneeweiss A, Kummel S, Denkert C, Mehta K, Loibl S, Untch M. Survival after adding capecitabine and trastuzumab to neoadjuvant anthracycline-taxane-based chemotherapy for primary breast cancer (GBG 40--GeparQuattro). Ann Oncol. 2014 Jan;25(1):81-9. doi: 10.1093/annonc/mdt410. Epub 2013 Nov 21.

  PMID: 24273046 DERIVED

• von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May 20;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595. Epub 2012 Apr 16.

  PMID: 22508812 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms

Interventions

Trastuzumab; Capecitabine; Cyclophosphamide; Docetaxel; Epirubicin; Chemotherapy, Adjuvant; Neoadjuvant Therapy

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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; 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; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Gunter von Minckwitz, MD

  GBG Forschungs GmbH

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 6, 2006
• First Posted: February 7, 2006
• Study Start: January 1, 2005
• Last Updated: August 26, 2013

Record last verified: 2009-07

Locations

DE (1)