Phase Ib Study of Gemcitabine Plus Cisplatin or Carboplatin Plus Dovitinib in Patients With Advanced Solid Tumors
Phase Ib Study of Dovitinib in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Plus Carboplatin in Patients With Advanced Solid Tumors
調査の概要
詳細な説明
This is a phase Ib study of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. This study will utilize standard 3+3 dose escalation rules to define the recommended phase II dose. Dose escalation will proceed independently in the two cohorts (cisplatin cohort: gemcitabine + cisplatin + dovitinib; carboplatin cohort: gemcitabine + carboplatin + dovitinib). Patients will receive treatment for up to 6 cycles, in the absence of toxicity, until disease progression
Primary Objective:
To determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin.
Secondary Objectives:
- To determine the response rate to treatment as per Response Evaluation Criteria in Solid Tumors (RECIST)
- To determine the toxicity of treatment at per the Common Terminology for Adverse Events (CTCAE v4)
- To determine the pharmacokinetics of dovitinib in combination with gemcitabine plus cisplatin or carboplatin.
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
-
-
New York
-
New York、New York、アメリカ、10029
- Icahn School of Medicine at Mount Sinai
-
-
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:
- Written informed consent and HIPAA authorization for release of personal health information.
- Age ≥ 18 years at the time of consent.
- Karnofsky Performance Status of ≥ 70%.
- Advanced/metastatic solid tumor for which treatment with gemcitabine plus carboplatin or gemcitabine plus cisplatin would otherwise be warranted.
- Prior treatment with chemotherapy is permitted. Patients must not have received more than three prior chemotherapeutic regimens.
Adequate organ function as determined by the following laboratory values:
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 100 x 109/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Creatinine of ≤ 1.5 OR Calculated creatinine clearance of ≥ 60 cc/min for the cisplatin cohort.
Calculated creatinine clearance of ≥ 30 cc/min for the carboplatin cohort.
- Bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST, SGOT) ≤ 1.5 ULN
- Alanine Aminotransferase (ALT, SGPT) < 1.5 ULN
- INR ≤ 1.5 and a PTT within normal limits
- LVEF assessed by 2-D echocardiogram (ECHO) > 50% or lower limit of normal or multiple gated acquisition scan (MUGA) > 45% or lower limit of normal
Exclusion Criteria:
- Prior treatment with more than three prior chemotherapy regimens.
- Has had major surgery within 30 days of starting the study treatment
- Have active CNS metastases.
- No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
- Prior cancer treatment must be completed at least 30 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxic effects of the regimen.
- Prior radiation therapy must be completed at least 30 days prior to being registered for protocol therapy.
- Pregnant or breastfeeding.
- Clinically significant infections as judged by the treating investigator.
- Impaired cardiac function or clinically significant cardiac diseases
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin
- Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception.
- Fertile males not willing to use contraception
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: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 |
|---|---|
|
アクティブコンパレータ:Cisplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts.
|
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts
他の名前:
|
|
アクティブコンパレータ:Carboplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts.
|
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19.
Treatment will be recycled every 21-days.
The dose of dovitinib will be escalated in successive cohorts
他の名前:
|
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 |
|---|---|---|
|
Recommended phase II dose of combination regimen
時間枠:Within the first 21 days of treatment
|
The primary objectives of this study are to determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus carboplatin or cisplatin.
|
Within the first 21 days of treatment
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Antitumor activity
時間枠:After every 2 cycles (42 days) of combination therapy up to 3 years
|
A CT scan of the chest, abdomen, and pelvis will be performed after every 2 cycles (or sooner if there is evidence of disease progression) while on combination therapy until disease progression (eg, after cycle 2, after cycle 4, and after cycle 6).
Response to treatment will be determined using RECIST.
|
After every 2 cycles (42 days) of combination therapy up to 3 years
|
協力者と研究者
スポンサー
協力者
捜査官
- 主任研究者:Matthew D. Galsky, M.D.、Icahn School of Medicine at Mount Sinai
出版物と役立つリンク
一般刊行物
- Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780.
- Knowles MA. Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors. Future Oncol. 2008 Feb;4(1):71-83. doi: 10.2217/14796694.4.1.71.
- Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, Morrison R, Fox JA, Heise C, Louie S, Aziz N, Garzon F, Michelson G, Judson IR, Jadayel D, Braendle E, de Bono JS. A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2008 Apr 1;14(7):2075-81. doi: 10.1158/1078-0432.CCR-07-1466.
研究記録日
主要日程の研究
研究開始
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 (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。