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

Metastatic Breast Cancer Clinical Trial

— TEX  

Official title:

Treatment With the Combination of Epirubicin and Paclitaxel Alone or Together With Capecitabine as First Line Treatment in Metastatic Breast Cancer. A Multicenter, Randomized Phase III Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01433614
• Other study ID #: TEX trial
• Status: Completed
• Phase: Phase 3
• First received: September 1, 2011
• Last updated: September 16, 2015
• Start date: December 2002
• Est. completion date: December 2013

Study information

• Verified date: September 2015
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: December 2013
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Epirubicin
75 mg/m2 i.v. every 3 weeks, both study arms
• Paclitaxel
175 mg/m2 i.v., every 3 weeks study arm A 155 mg/m2 i.v., every 3 weeks study arm B
• Capecitabine
1650 mg/m2 p.o. days 1-14 every 3 weeks study arm B

Locations

Country	Name	City	State
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Helsingborg Gen. Hospital	Helsingborg
Sweden	Kalmar Central Hospital	Kalmar
Sweden	Karlstad Gen. Hospital	Karlstad
Sweden	Linköping University Hospital	Linköping
Sweden	Lund University Hospital	Lund
Sweden	Malmö General University Hospital	Malmö
Sweden	Sundsvall Gen. Hospital	Sundsvall
Sweden	Norrland University Hospital	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Hatschek

Country where clinical trial is conducted

Sweden, 

References & Publications (9)

Bjöhle J, Bergqvist J, Gronowitz JS, Johansson H, Carlsson L, Einbeigi Z, Linderholm B, Loman N, Malmberg M, Söderberg M, Sundquist M, Walz TM, Fernö M, Bergh J, Hatschek T. Serum thymidine kinase activity compared with CA 15-3 in locally advanced and met — View Citation

Hatschek T, Carlsson L, Einbeigi Z, Lidbrink E, Linderholm B, Lindh B, Loman N, Malmberg M, Rotstein S, Söderberg M, Sundquist M, Walz TM, Hellström M, Svensson H, Aström G, Brandberg Y, Carstensen J, Fernö M, Bergh J. Individually tailored treatment with — View Citation

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, Malmström PO, Söderberg M, Walz TM, Fernö M, Hatschek T, Hedenfalk I; TEX study group. Transcriptional P — View Citation

Kimbung S, Kovács A, Bendahl PO, Malmström P, Fernö 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.molo — View Citation

Suzuki C, Blomqvist L, Hatschek T, Carlsson L, Einbeigi Z, Linderholm B, Lindh B, Loman N, Malmberg M, Rotstein S, Söderberg M, Sundqvist M, Walz TM, Aström G, Fujii H, Jacobsson H, Glimelius B. Impact of the first tumor response at eight weeks on overall — View Citation

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. — View Citation

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 — View Citation

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/s — View Citation

Tobin NP, Harrell JC, Lövrot J, Egyhazi Brage S, Frostvik Stolt M, Carlsson L, Einbeigi Z, Linderholm B, Loman N, Malmberg M, Walz T, Fernö M, Perou CM, Bergh J, Hatschek T, Lindström LS; TEX Trialists Group. Molecular subtype and tumor characteristics of — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to treatment failure	Time on treatment irrespective of reason for disruption (toxicity, patients wish)	From date of randomization until date of treatment disruption for any reason up to 78 months
Secondary	Response rate		Every 9 weeks during treatment
Secondary	Overall survival	Date and cause of death reported yearly during the ongoing trial, up to 78 months after primary completion date only on the occasion of death	Time from randomisation until date of death up to 78 months
Secondary	Number of participants with adverse events	All side effects which appear during treatment are reported and graded according CTC v.2.	Continuously during treatment and until 2 months after termination
Secondary	Quality of life	Measured at five points during nine months from randomization.	Baseline, 2, 4, 6 and 9 months
Secondary	Tumor biological data related to treatment	Fine needle aspirates from metastases	Within two weeks before start of treatment

External Links

•   Swedish website for the study members, password required.