Monotherapy Dose Finding With BI 847325 in Solid Tumours
An Open Label Phase Ia/Ib Study of Two Dosing Schedules of BI 847325, Orally Administered Once a Day in Patients With Advanced Solid Tumours, With Repeated Cyclic Administration in Patients With Clinical Benefit
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Bruxelles、ベルギー
- 1287.1.3201 Boehringer Ingelheim Investigational Site
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Leuven、ベルギー
- 1287.1.3202 Boehringer Ingelheim Investigational Site
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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
Inclusion criteria:
- Patients with a histologically or cytologically confirmed diagnosis of an advanced unresectable and/or metastatic solid tumour, and who have failed conventional treatment or for whom no therapy of proven efficacy exists or who are not amenable to standard therapies.
- Age 18 years and older
- Written informed consent consistent with International conference on harmonization - Good clinical practice (ICH-GCP) and local legislation
- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
- Recovery of therapy-related toxicities from previous anti-tumour therapies to Common Terminology Criteria for Adverse Events (CTCAE) = grade 1 (with the exception of alopecia).
- Written informed consent to the use of archival tumour sample for determination of the BRAF/Tat sarcoma viral oncogene homolog (RAS) mutational status.
- Life expectancy of at least 12 weeks.
In escalation phase, when pharmacokinetic (PK) close to predicted Cmax or when signs of progressive disease (PD) modulation present, optional tumour biopsies (at same timepoints as in expansion phase) for the patients who consented to it.
In addition, all patients included in the expansion phase (part Ib) must:
- have been diagnosed with one of the following tumours: melanoma, colorectal carcinoma, Non Small Cell Lung Cancer (NSCLC) or exocrine pancreas adenocarcinoma, and have been shown on their archival tumour sample to have KRAS or BRAF mutation.
- have a measurable disease.
- have documented/proven progressive disease within the last 6 months, according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria
11. have a tumour lesion accessible for biopsies (pre- and post-treatment): this is mandatory for patients with colorectal carcinoma or melanoma, optional for patients with NSCLC or exocrine pancreas adenocarcinoma.
Exclusion criteria:
- Inability to swallow tablets.
- Additional other serious illness , concomitant non-oncological disease (e.g. active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV), or ongoing toxicity from prior therapies considered by the investigator to potentially compromise patient's safety in this trial.
- Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the last 28 days.
- Second malignancy currently requiring another anti-cancer therapy.
- Absolute neutrophil count less than 1500/mm3.
- Platelet count less than 100 000/mm3.
- Bilirubin greater than 1.5 mg/dL (>26 µmol/L, Système international (SI) unit equivalent) (except known Gilbert's syndrome).
- Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases, greater than five times the upper limit of normal).
- Serum creatinine greater than 1.5 mg/dL (>132 µmol/L, SI unit equivalent).
- Previous episode of QT prolongation due to a medication which, as a result of it, had to be discontinued; or long QT syndrome; or corrected QT interval (QTc) with Fridericia's correction >480 msec on screening ECG.
- Pregnancy or breastfeeding.
- Women or men who are sexually active and unwilling to use a medically acceptable method of contraception.
- Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks before start of therapy or concomitant with this trial.
- Systemic anti-cancer therapy or radiotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to Luteinizing hormone-releasing hormone (LHRH) agonists, steroids and bisphosphonates.
- Patients unable to comply with the protocol.
- Active alcohol or drug abuse.
- history or presence of cardiovascular abnormalities deemed clinically relevant by the investigator. Myocardial infarction within 6 months prior to study.
- Cardiac left ventricular ejection fraction <50% or less than institutional lower limit of normal by Multiple Gated Acquisition scan (MUGA) or echocardiography
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:非ランダム化
- 介入モデル:単一グループの割り当て
- 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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実験的:arm A
14 days once a day oral intake of BI 847325 followed by 7 days break in 3-week cycles
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low to high dose
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実験的:arm B
5 days once daily oral intake of BI 847325 followed by 2 days break, repeated every week
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low to high dose
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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 |
---|---|---|
Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study
時間枠:3 weeks
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Occurrence of dose limiting toxicity (DLT) during the first treatment cycle for the treatment Schedules A and B. Some patients excluded from Treated Set (TS) as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients. |
3 weeks
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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 |
---|---|---|
Best Overall Response
時間枠:From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013
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Best overall response was the best response a patient experienced during their time on study from the start of treatment until: disease progression, the last evaluable assessment in the absence of progression, or the start of subsequent anti-cancer therapy.
Death was not considered as progressive disease when determining best overall response; patients who died prior to an evaluable imaging assessment were reported as not evaluable.
Some patients were excluded from TS as they were not evaluable for determination of maximum tolerated dose.
Thus the number of evaluable TS patients are not the same as the number of original TS patients.
|
From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013
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Objective Response
時間枠:From the start of treatment and the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
|
Objective response was a best overall response of complete or partial response, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment. Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients. |
From the start of treatment and the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
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Disease Control
時間枠:From the start of treatment to the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
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Disease control was a best overall response of complete response, partial response or stable disease, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment.
Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose.
Thus the number of evaluable TS patients are not the same as the number of original TS patients.
|
From the start of treatment to the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
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協力者と研究者
スポンサー
出版物と役立つリンク
便利なリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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 (実際)
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
本研究に関する用語
その他の研究ID番号
- 1287.1
- 2010-023832-18 (EudraCT番号:EudraCT)
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。
day 1 to day 14の臨床試験
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