Epirubicin and Paclitaxel, Alone or Together With Capecitabine as First Line Treatment in Metastatic Breast Cancer (TEX)
2015年9月16日 更新者：Thomas Hatschek
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
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).
調査の概要
研究の種類
介入
入学 (実際)
304
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Göteborg、スウェーデン
- Sahlgrenska University Hospital
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Helsingborg、スウェーデン
- Helsingborg Gen. Hospital
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Kalmar、スウェーデン
- Kalmar Central Hospital
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Karlstad、スウェーデン
- Karlstad Gen. Hospital
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Linköping、スウェーデン
- Linköping University Hospital
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Lund、スウェーデン
- Lund University Hospital
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Malmö、スウェーデン
- Malmö General University Hospital
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Sundsvall、スウェーデン
- Sundsvall Gen. Hospital
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Umeå、スウェーデン
- Norrland University Hospital
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
女性
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：Epirubicin + paclitaxel (Taxol)
Epirubicin 75mg/m2 i.v., paclitaxel 175 mg/m2 i.v. on day 1 every 21 days.
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75 mg/m2 i.v.
every 3 weeks, both study arms
175 mg/m2 i.v., every 3 weeks study arm A 155 mg/m2 i.v., every 3 weeks study arm B
他の名前：
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アクティブコンパレータ：Paclitaxel + epirubicin + capecitabine
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.
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75 mg/m2 i.v.
every 3 weeks, both study arms
175 mg/m2 i.v., every 3 weeks study arm A 155 mg/m2 i.v., every 3 weeks study arm B
他の名前：
1650 mg/m2 p.o. days 1-14 every 3 weeks study arm B
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Time to progression
時間枠：From date of randomisation until date of first radiolocically documented progression or death from any cause, whichever comes first up to 78 months
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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
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From date of randomisation until date of first radiolocically documented progression or death from any cause, whichever comes first up to 78 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Time to treatment failure
時間枠：From date of randomization until date of treatment disruption for any reason up to 78 months
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Time on treatment irrespective of reason for disruption (toxicity, patients wish)
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From date of randomization until date of treatment disruption for any reason up to 78 months
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Response rate
時間枠：Every 9 weeks during treatment
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Every 9 weeks during treatment
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Overall survival
時間枠：Time from randomisation until date of death up to 78 months
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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
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Time from randomisation until date of death up to 78 months
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Number of participants with adverse events
時間枠：Continuously during treatment and until 2 months after termination
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All side effects which appear during treatment are reported and graded according CTC v.2.
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Continuously during treatment and until 2 months after termination
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Quality of life
時間枠：Baseline, 2, 4, 6 and 9 months
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Measured at five points during nine months from randomization.
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Baseline, 2, 4, 6 and 9 months
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Tumor biological data related to treatment
時間枠：Within two weeks before start of treatment
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Fine needle aspirates from metastases
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Within two weeks before start of treatment
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Thomas Hatschek, PhD、Karolinska University Hospital
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2002年12月1日
一次修了 (実際)
2006年6月1日
研究の完了 (実際)
2013年12月1日
試験登録日
最初に提出
2011年9月1日
QC基準を満たした最初の提出物
2011年9月13日
最初の投稿 (見積もり)
2011年9月14日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年9月17日
QC基準を満たした最後の更新が送信されました
2015年9月16日
最終確認日
2015年9月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- TEX trial
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