このページは自動翻訳されたものであり、翻訳の正確性は保証されていません。を参照してください。 英語版 ソーステキスト用。

R(+)XK469 in Treating Patients With Advanced Neuroblastoma

2013年12月13日 更新者：National Cancer Institute (NCI)

Phase I Study Of R(+)XK469 In Patients With Advanced Neuroblastoma

This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

OBJECTIVES:

I. Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.

II. Determine the safety of this drug in these patients. III. Determine the tolerance to this drug in these patients. IV. Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.

V. Determine, preliminarily, any antineoplastic activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

SCHEDULE A: Patients receive R(+)XK469 intravenously (IV) over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.

研究の種類

介入

入学 (実際)

85

段階

  • フェーズ 1

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

  • アメリカ
    • Illinois
      • Chicago、Illinois、アメリカ、60637-1470
        • University of Chicago Comprehensive Cancer Center

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

5年～20年 (子、大人)

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

全て

説明

Inclusion Criteria:

  • Histologically confirmed high-risk neuroblastoma that has relapsed or is refractory to standard therapy

  • No active brain metastases

    • Previously treated brain metastases allowed if there is no requirement for corticosteroids or anticonvulsants
  • Performance status - Karnofsky performance status 70-100% or Lansky score ≥ 70 for your pediatric patients
  • More than 3 months
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin normal (unless due to documented Gilbert's syndrome)
  • Creatinine less than 1.5 times upper limit of normal
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other concurrent uncontrolled illness that would preclude study participation
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study participation
  • No prior allergic reaction to compounds of similar chemical or biological composition to study drug (e.g., flurbiprofen or ibuprofen)
  • No HIV-positive patients
  • No concurrent biologic agents
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • No other concurrent chemotherapy
  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • No concurrent palliative radiotherapy
  • See Disease Characteristics
  • Recovered from all prior therapy
  • No other concurrent investigational agents
  • No concurrent commercial agents or therapies directed at malignancy
  • No concurrent combination anti-retroviral therapy for HIV-positive patients

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：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
実験的：Treatment (chemotherapy)

SCHEDULE A: Patients receive R(+)XK469 IV over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.
薬：R(+)XK469
与えられた IV
他の名前：
  • XK469

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
Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
時間枠：Day 29 of course 1
Defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) was less than 33%.
Day 29 of course 1
DLT
時間枠：Day 29 of course 1
Defined as the occurrence of any of the following: 1) grade 3 or higher nonhematologic toxicity except fatigue, alopecia, nausea, vomiting, 2) grade 4 thrombocytopenia or anemia, 3) any fever accompanied by granulocyte count < 1000/mm^3 (grade 3 or 4 neutropenia), 4) failure to recover absolute neutrophil count 1500/μL
Day 29 of course 1
Recommended phase II dose
時間枠：Day 29 of course 1
Generally defined as the MTD. For both schedules A and B and the pediatric dosing schedule, once the recommended phase II dose has been tentatively defined, a total of 12 evaluable patients will be studied to ensure the feasibility of this dose for phase II trials. If interindividual pharmacokinetic variability is high, additional patients will be enrolled (maximum of 20 at the phase II dose) to permit adequate pharmacological characterization of XK469 and the relationship of interindividual pharmacokinetic variability to toxicity.
Day 29 of course 1

二次結果の測定

結果測定
メジャーの説明
時間枠
Metabolism of XK469 in pediatric patients
時間枠：Days 1-3 of course 1
Performed by high-performance liquid chromatography (HPLC). Plasma metabolic ratios between metabolite and XK469 concentrations will be used as an index of metabolic activity and phenotype for each patient. The modality of the frequency distribution of metabolic ratios will be also described.
Days 1-3 of course 1
Pharmacokinetics of XK469 in pediatric patients
時間枠：Days 1-3 of course 1
The maximum number of samples for pharmacokinetic studies will not exceed 20. Analyzed by non compartmental method using the WinNonlin software. Parameters include the elimination rate constant, the area under the concentration vs. time curve (AUC), terminal half-life, total (nonrenal + renal) clearance, and volume of distribution at steady state. Mean, standard deviation, and coefficient of variation will be determined for each parameter.
Days 1-3 of course 1
Pharmacodynamics of XK469 in pediatric patients
時間枠：Continuously over the course of study treatment
Performed by correlating area under the curve (AUC) (and other parameters) of R(+)XK469 and metabolites with observed toxicities. Specifically, we will compare the AUC in those patients who experience grade >= 2 toxicity to those who experience grade < 2 toxicity using a Wilcoxon, nonparametric rank-sum test.
Continuously over the course of study treatment
Antineoplastic activity of XK469 for neuroblastoma
時間枠：Every 2 courses
Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Every 2 courses

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

National Cancer Institute (NCI)

捜査官

  • 主任研究者：Susan Cohn、University of Chicago Comprehensive Cancer Center

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

2001年12月1日

一次修了 (実際)

2009年9月1日

試験登録日

最初に提出

2002年1月4日

QC基準を満たした最初の提出物

2003年1月26日

最初の投稿 (見積もり)

2003年1月27日

学習記録の更新

投稿された最後の更新 (見積もり)

2013年12月16日

QC基準を満たした最後の更新が送信されました

2013年12月13日

最終確認日

2013年12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

  • NCI-2009-00013 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
  • U01CA069852 (米国 NIH グラント/契約)
  • UCCRC-11108B
  • CDR0000739128
  • NCI-4570
  • 11108B (その他の識別子：University of Chicago Comprehensive Cancer Center)
  • 4570 (その他の識別子：CTEP)

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。

購読する