A Double Blind Randomised Study of Lapatinib and Placebo in Metastatic TCC of the Urothelium (LaMB)
A Phase II/III, Randomised, Two-Arm, Comparison of Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With HER1 and/or HER2 Overexpressing Locally Advanced or Metastatic Bladder Cancer [LaMB]
RATIONALE: Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether lapatinib ditosylate is more effective than a placebo in killing tumor cells.
PURPOSE: This randomized phase II/III trial is studying how well lapatinib ditosylate works compared to a placebo in treating patients with stage IV bladder cancer.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Compare progression-free survival in patients with HER1- and/or HER2-overexpressing stage IV bladder cancer who have been randomized to maintenance therapy with lapatinib ditosylate or placebo following first-line chemotherapy.
Secondary
- Compare overall survival between these patient groups.
- Evaluate the safety and tolerability of the regimens in these patients.
- Assess and compare quality of life between these patient groups.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status and response to first line chemotherapy (complete or partial response vs stable disease). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral placebo once daily in the absence of disease progression or unacceptable toxicity.
Patients undergo quality of life assessment by EORTC QLQ-C30 at baseline and every 4 weeks during study treatment.
After completion of study treatment, patients are followed up periodically for up to 5 years.
研究の種類
入学 (予想される)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究場所
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Aberdeen、イギリス
- NHS Grampian - Aberdeen Royal Infirmary
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Basildon、イギリス
- Basildon and Thurrock University Hospital NHS Trust - Basildon Hospital
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Birmingham、イギリス
- University Hospitals Birmingham NHS Foundation Trust - Birmingham University Hospital
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Bournemouth、イギリス
- Royal Bournemouth and Christchurch NHS Foundation Trust - Royal Bournemouth Hospital
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Bristol、イギリス
- University Hospitals Bristol NHS Trust - Bristol University Hospital
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Cambridge、イギリス
- Cambridge University Hospitals NHS Trust - Addenbrooke's Hospital
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Chelmsford、イギリス
- Mid Essex NHS Trust - Broomfield Hospital
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Colchester、イギリス
- Colchester University Hospitals NHS Trust
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Coventry、イギリス
- University Hospitals Coventry & Warwickshire NHS Trust
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Derby、イギリス
- Derby Hospitals NHS Trust - Royal Derby Hospital
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Glasgow、イギリス
- NHS Greater Glasgow and Clyde - The Beatson
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Huddersfield、イギリス
- Calderdale and Huddersfield NHS Trust - Huddersfield Royal Infirmary
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Ipswich、イギリス
- Ipswich Hospital NHS Trust
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Leicester、イギリス
- University Hospitals of Leicester NHS Trust
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Liverpool、イギリス
- Clatterbridge Centre for Oncology NHS Trust
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London、イギリス
- Imperial Healthcare NHS Trust
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London、イギリス
- Guys & St Thomas' Hospital NHS Trust - Guys Hospital
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London、イギリス
- Royal Marsden NHS Trust
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Middlesborough、イギリス
- South Tees NHS Trust - James Cook University Hospital
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Newcastle、イギリス
- Newcastle Upon Tyne Hospitals NHS Trust
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Northampton、イギリス
- Northampton General Hospitals NHS Trust
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Nottingham、イギリス
- Nottingham University Hospitals NHS Trust
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Nottingham、イギリス
- Sherwood Forest Hospitals NHS Trust - Kings Mill Hospital
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Portsmouth、イギリス
- Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
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Romford、イギリス
- Barking, Havering and Redbridge NHS Trust - Queens Hospital
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Taunton、イギリス
- Taunton and Somerset NHS Trust - Musgrove Park Hospital
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England
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London、England、イギリス、EC1M 6BQ
- Barts and the London NHS Trust
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
DISEASE CHARACTERISTICS:
Histologically confirmed transitional cell carcinoma of the bladder
- Stage IV disease
- Metastatic or locally advanced disease
HER1- and/or HER2-positive disease, defined by the following criteria:
- 2+ or 3+ intensity on IHC
- Able to commence the study treatment within 10 weeks of completing chemotherapy
Must have achieved objective response or stable disease following 4-8 courses of first-line chemotherapy
- No progression with first-line chemotherapy for metastatic disease
- Any widely accepted chemotherapy regimen for bladder cancer allowed
- Patients who did not receive cisplatin are eligible
PATIENT CHARACTERISTICS:
- ECOG performance status 0-3
- ANC ≥ 1.0 x 10^9/L
- Hemoglobin ≥ 8.0 g/dL
- Platelet count ≥ 75 x 10^9/L
- ALT/AST < 2 times upper limit of normal (ULN)
- Bilirubin < 1.5 times ULN
- Serum creatinine ≤ 3.0 ULN AND/OR creatinine clearance ≥ 30 mL/min
- LVEF ≥ 50% (as assessed by quantitative echocardiogram or MUGA)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
No current active hepatic or biliary disease, except for any of the following:
- Gilbert's syndrome
- Asymptomatic gallstones
- Liver metastases
- Stable chronic liver disease per investigator assessment
- No known hypersensitivity to the study medication
No history of prior or concurrent other neoplasms, except for:
- Any non life-threatening tumours that have been curatively treated.
- Prostate cancer isolated to the prostate gland
No significant cardiac disease, including any of the following:
- Angina pectoris
- Severe cardiac arrhythmia requiring medication
- Severe conduction abnormalities
- Clinically significant valvular disease
- Cardiomegaly
- Prior myocardial infarction
- Ventricular hypertrophy
- Congestive heart failure
- Poorly uncontrolled hypertension (resting diastolic blood pressure > 115 mm Hg)
- Other cardiomyopathy
- No serious intercurrent medical or psychiatric illness
- No serious active infection
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No more than 1 line of prior chemotherapy for metastatic or locally advanced disease (neoadjuvant/adjuvant chemotherapy allowed)
- No more than 10 weeks since first-line chemotherapy
- No prior lapatinib ditosylate
- No prior radiotherapy to the indicator lesion(s) (newly arising lesions in previously irradiated areas allowed)
At least 14 days since prior and no concurrent CYP3A4 inducers, including but not limited to, any of the following:
- Antibiotics (all rifamycin class agents [e.g., rifampicin, rifabutin, rifapentine])
- Anticonvulsants (phenytoin, carbamazepine, barbiturates [e.g., phenobarbital])
- Oral glucocorticoids (cortisone [> 50 mg], hydrocortisone [> 40 mg], prednisone [> 10 mg], methylprednisolone [> 8 mg], dexamethasone [> 2 mg²])
- St. John's wort or modafinil
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including but not limited to, any of the following:
- Antibiotics (clarithromycin, erythromycin, troleandomycin)
- Antifungals (itraconazole, ketoconazole, fluconazole [>150 mg daily], voriconazole)
- Antiretrovirals/protease inhibitors (delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir)
- Calcium channel blockers (verapamil, diltiazem)
- Antidepressants (nefazodone, fluvoxamine)
- Gastrointestinal agents (cimetidine, aprepitant)
- Grapefruit, grapefruit juice
- At least 6 months since prior and no concurrent amiodarone
- No concurrent radical or curative therapy (radiotherapy or surgery) at the end of first-line treatment (palliative radiotherapy allowed)
- No other concurrent experimental or investigational drugs
- No other concurrent anticancer treatment, including cytotoxic or specific immune therapy
研究計画
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:ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的:Arm I
Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity.
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経口投与
他の名前:
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プラセボコンパレーター:Arm II
Patients receive oral placebo once daily in the absence of disease progression or unacceptable toxicity.
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経口投与
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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 |
時間枠 |
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Progression free survival
時間枠:Disease Progression - at least 20% increase in the sum of longest diameters of target lesions.
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Disease Progression - at least 20% increase in the sum of longest diameters of target lesions.
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二次結果の測定
結果測定 |
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全生存
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協力者と研究者
協力者
捜査官
- 主任研究者:Thomas Powles, MD, MRCP、Queen Mary University of London
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
膀胱がんの臨床試験
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