Epirubicin and Paclitaxel, Alone or Together With Capecitabine as First Line Treatment in Metastatic Breast Cancer

NCT01433614 | Completed Phase 3 DMC

• 1 other identifier: TEX trial
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 9

Brief Summary

Anthracycline-taxane regimens are effective means of postponing progression in metastatic breast cancer. It is yet unclear whether addition of capecitabine to this combination improves the treatment outcome. Patients with advanced breast cancer are randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin®) and paclitaxel (Taxol®) alone (ET) or in combination with capecitabine (Xeloda®, TEX). Starting doses for ET are epirubicin 75 mg/m2 plus paclitaxel 175 mg/m2, and for TEX epirubicin 75mg/m2, paclitaxel 155 mg/m2, and capecitabine 825 mg/m2 BID for 14 days. Subsequently, doses are tailored related to side effects. Primary endpoint is progression-free survival (PFS); secondary endpoints are overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL).

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Time to progression

  Time to progression comparing treatment with ET vs. TEX in patients with advanced breast cancer. Evaluation every 9 weeks during treatment until progression as long as study treatment was given, and every 12 weeks until date of progression, if treatment was disrupted for any other reason. Patients in the state of persistent complete response after primary completion date were reported only upon date of progression or death up to 78 months

  From date of randomisation until date of first radiolocically documented progression or death from any cause, whichever comes first up to 78 months

Secondary Outcomes (6)

• Time to treatment failure

  From date of randomization until date of treatment disruption for any reason up to 78 months

• Response rate

  Every 9 weeks during treatment

• Overall survival

  Time from randomisation until date of death up to 78 months

• Number of participants with adverse events

  Continuously during treatment and until 2 months after termination

• Quality of life

  Baseline, 2, 4, 6 and 9 months

Study Arms (2)

Epirubicin + paclitaxel (Taxol)

ACTIVE COMPARATOR

Epirubicin 75mg/m2 i.v., paclitaxel 175 mg/m2 i.v. on day 1 every 21 days.

Drug: Epirubicin; Drug: Paclitaxel

Paclitaxel + epirubicin + capecitabine

ACTIVE COMPARATOR

Paclitaxel 155 mg/m2 i.v., epirubicin 75 mg/m2 i.v day 1, capecitabine 1650 mg/m2 p.o. on days 1-14 every 21 days.

Drug: Epirubicin; Drug: Paclitaxel; Drug: Capecitabine

Interventions

Epirubicin DRUG

75 mg/m2 i.v. every 3 weeks, both study arms

Epirubicin + paclitaxel (Taxol); Paclitaxel + epirubicin + capecitabine

Paclitaxel DRUG

175 mg/m2 i.v., every 3 weeks study arm A 155 mg/m2 i.v., every 3 weeks study arm B

Also known as: Taxol

Epirubicin + paclitaxel (Taxol); Paclitaxel + epirubicin + capecitabine

Capecitabine DRUG

1650 mg/m2 p.o. days 1-14 every 3 weeks study arm B

Also known as: Xeloda

Paclitaxel + epirubicin + capecitabine

Eligibility Criteria

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

You may qualify if:

• Morphologically proven breast carcinoma
• Written patient consent must be obtained
• Measurable disease (i.e. at least one lesion that can be accurately measured in at least one dimension as ≥20 mm by conventional techniques, or as ≥10 mm by spiral CT scan) as defined in section 8.
• Lytic and blastic bone metastases as only site of recurrence are allowed
• Age 18 years or older
• ECOG performance status 0-2
• Life expectancy of at least three months
• Adequate cardiac functions
• Adequate hematological, renal and hepatic functions
• Patient must be accessible for treatment and follow-up.

You may not qualify if:

• Treatment-free interval less than one year, if previous adjuvant, neoadjuvant or after radically treated locoregional recurrence given regimen contained anthracycline, taxane or capecitabine. This limitation does not apply for regimens containing other than the drugs mentioned
• During adjuvant treatment obtained cumulative doses exceeding 375 mg/m2 for doxorubicin, or 550 mg/m2 for epirubicin, abnormal ECG or reduced cardiac function measured by left ventricular ejection fraction (LVEF).
• Indication for the use of trastuzumab (Herceptin) as first-line treatment in patients with tumor overexpressing c-erbB2.
• Any previous chemotherapy for metastatic disease, except for radically treated locoregional relapse
• Neoplasm other than breast carcinoma, except for non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix, diagnosed during the past five years
• Pregnancy or lactation
• Known brain metastases
• History of atrial or ventricular arrhythmias and/or congestive heart failure, even if medically controlled. History of clinical and electrocardiographically documented myocardial infarction
• Preexisting motor or sensory neuropathy ≥ grade 2 according to NCI CTC 2.0 criteria (severe paresthesia and/or mild weakness, or worse)
• Severe hepatic or renal impairment (for capecitabine: calculated creatinine clearance below 30 ml/min; for calculation, see p. 5.1.4) not allowing for adequate use of the proposed regimens
• History of known dihydropyrimidine dehydrogenase (DPD) deficiency (severe reaction on previous treatment with fluorouracil, e.g experience of mucositis, hand-foot syndrome, or diarrhea)
• Active infection or other serious underlying medical condition which would impair the ability of the patient to receive protocol treatment, including prior allergic reactions to drugs containing cremophor, such as teniposide, cyclosporin or vitamin K
• Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent.

Sponsors & Collaborators

• Thomas Hatschek: lead

Study Sites (9)

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Helsingborg Gen. Hospital

Helsingborg, Sweden

Location

Kalmar Central Hospital

Kalmar, Sweden

Location

Karlstad Gen. Hospital

Karlstad, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Lund University Hospital

Lund, Sweden

Location

Malmö General University Hospital

Malmo, Sweden

Location

Sundsvall Gen. Hospital

Sundsvall, Sweden

Location

Norrland University Hospital

Umeå, Sweden

Location

Related Publications (10)

• Svensson H, Brandberg Y, Einbeigi Z, Hatschek T, Ahlberg K. Psychological reactions to progression of metastatic breast cancer--an interview study. Cancer Nurs. 2009 Jan-Feb;32(1):55-63. doi: 10.1097/01.NCC.0000343374.09270.ff.

  PMID: 19104202 RESULT

• Svensson H, Einbeigi Z, Johansson H, Hatschek T, Brandberg Y. Quality of life in women with metastatic breast cancer during 9 months after randomization in the TEX trial (epirubicin and paclitaxel w/o capecitabine). Breast Cancer Res Treat. 2010 Oct;123(3):785-93. doi: 10.1007/s10549-010-1084-8. Epub 2010 Aug 3.

  PMID: 20680680 RESULT

• Svensson H, Hatschek T, Johansson H, Einbeigi Z, Brandberg Y. Health-related quality of life as prognostic factor for response, progression-free survival, and survival in women with metastatic breast cancer. Med Oncol. 2012 Jun;29(2):432-8. doi: 10.1007/s12032-011-9844-9. Epub 2011 Feb 6.

  PMID: 21298494 RESULT

• Hatschek T, Carlsson L, Einbeigi Z, Lidbrink E, Linderholm B, Lindh B, Loman N, Malmberg M, Rotstein S, Soderberg M, Sundquist M, Walz TM, Hellstrom M, Svensson H, Astrom G, Brandberg Y, Carstensen J, Ferno M, Bergh J. Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial. Breast Cancer Res Treat. 2012 Feb;131(3):939-47. doi: 10.1007/s10549-011-1880-9. Epub 2011 Nov 18.

  PMID: 22094937 RESULT

• Suzuki C, Blomqvist L, Hatschek T, Carlsson L, Einbeigi Z, Linderholm B, Lindh B, Loman N, Malmberg M, Rotstein S, Soderberg M, Sundqvist M, Walz TM, Astrom G, Fujii H, Jacobsson H, Glimelius B. Impact of the first tumor response at eight weeks on overall survival in metastatic breast cancer patients treated with first-line combination chemotherapy. Med Oncol. 2013 Mar;30(1):415. doi: 10.1007/s12032-012-0415-5. Epub 2013 Jan 16.

  PMID: 23322522 RESULT

• Bjohle J, Bergqvist J, Gronowitz JS, Johansson H, Carlsson L, Einbeigi Z, Linderholm B, Loman N, Malmberg M, Soderberg M, Sundquist M, Walz TM, Ferno M, Bergh J, Hatschek T. Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial. Breast Cancer Res Treat. 2013 Jun;139(3):751-8. doi: 10.1007/s10549-013-2579-x. Epub 2013 Jun 5.

  PMID: 23736998 RESULT

• Tobin NP, Harrell JC, Lovrot J, Egyhazi Brage S, Frostvik Stolt M, Carlsson L, Einbeigi Z, Linderholm B, Loman N, Malmberg M, Walz T, Ferno M, Perou CM, Bergh J, Hatschek T, Lindstrom LS; TEX Trialists Group. Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival. Ann Oncol. 2015 Jan;26(1):81-88. doi: 10.1093/annonc/mdu498. Epub 2014 Oct 31.

  PMID: 25361981 RESULT

• Kimbung S, Kovacs A, Bendahl PO, Malmstrom P, Ferno M, Hatschek T, Hedenfalk I. Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences. Mol Oncol. 2014 Feb;8(1):119-28. doi: 10.1016/j.molonc.2013.10.002. Epub 2013 Oct 14.

  PMID: 24287398 RESULT

• Kimbung S, Johansson I, Danielsson A, Veerla S, Egyhazi Brage S, Frostvik Stolt M, Skoog L, Carlsson L, Einbeigi Z, Lidbrink E, Linderholm B, Loman N, Malmstrom PO, Soderberg M, Walz TM, Ferno M, Hatschek T, Hedenfalk I; TEX study group. Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer. Clin Cancer Res. 2016 Jan 1;22(1):146-57. doi: 10.1158/1078-0432.CCR-15-0487. Epub 2015 Aug 14.

  PMID: 26276891 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

Epirubicin; Paclitaxel; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Thomas Hatschek, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 14, 2011
• Study Start: December 1, 2002
• Primary Completion: June 1, 2006
• Study Completion: December 1, 2013
• Last Updated: September 17, 2015

Record last verified: 2015-09

Locations

SE (9)