KRN5500 in Treating Patients With Solid Tumors
A Phase I Trial of KRN5500 (NSC 650426) Given as a 72 Hour Continuous IV Infusion Every 21 Days in Patients With Solid Tumors
調査の概要
詳細な説明
PRIMARY OBJECTIVES:
I. To establish the MTD and identify the DLTs of the investigational agent KRN5500 when administered by a 72-hr continuous i.v. infusion to patients with solid tumors who have failed standard therapy or for whom no standard therapy exists.
II. To establish and assess the safety of an appropriate dose for phase II studies.
III. To characterize the pharmacokinetics of KRN5500 in patients when administered by a 72 hr continuous IV infusion.
IV. To characterize the response to KRN5500 by FLT-PET scanning at the MTD.
SECONDARY OBJECTIVES:
I. To describe any preliminary evidence of antitumor activity. II. Establish pharmacodynamic relationships for the pharmacological effect of the drug upon surrogate markers of activity and host toxicity.
III. To compare the toxicity profiles for the 1 hr i.v. infusion and 72 hr continuous i.v. infusion administration schedules.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive KRN5500 IV over 24-72 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-3 patients receive KRN5500 at the starting dose over escalating infusion durations. After the longest duration of infusion time is safely reached, cohorts of 3-6 patients receive escalating doses of KRN5500 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with KRN5500 at the recommended phase II dose.
Patients are followed every 4 weeks until resolution of all toxicity.
PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12 months.
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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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Dana-Farber Cancer Institute
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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:
- Metastatic or inoperable malignancy, other than leukemia or a primary CNS tumor, for which there is no known curative or survival prolonging palliative therapy, or all such therapies have failed
- Life expectancy >= 2 months
- ECOG performance status =< 2
- WBC >= 3,000/mm^3
- ANC >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- SGOT ≤ 2.5-times the upper limit of normal (ULN)
- SGPT ≤ 2.5-times the ULN
- Total bilirubin ≤ 1.5 mg/dl
- Serum creatinine ≤ 1.5 mg/dl
- ECG showing no evidence of acute ischemia or serious conduction abnormality
- >= 2 weeks since major surgery
- >= 3 weeks since chemotherapy or radiation therapy, except for nitrosoureas and mitomycin-C, in which case the interval shall be 6 weeks
- Women of childbearing potential must not be pregnant or lactating; all women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of β-HCG) within 72 hr prior to receiving the study medication; KRN5500 has antiproliferative effects which may be harmful to the developing fetus or nursing infant
- Fertile males and females must use adequate contraception
- Central venous catheter placed at least one day prior to treatment
- Signed informed consent
Exclusion Criteria:
- A serious uncontrolled medical disorder or active infection that would impair the ability of the patient to receive study treatment
- Uncontrolled or significant pulmonary or cardiovascular disease, including a recent (6 months or less) myocardial infarction, any significant degree of congestive heart failure with or without medical treatment, any history of clinically significant atrial or ventricular arrhythmias, any history of second or third degree heart block, or prolonged QTc interval (greater than 450 ms) on electrocardiogram
- Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirement for steroids, or clinical symptoms related to brain metastases
- A psychiatric illness that precludes the ability to provide informed consent
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：なし
- 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：Treatment (KRN5500)
Patients receive KRN5500 IV over 24-72 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-3 patients receive KRN5500 at the starting dose over escalating infusion durations. After the longest duration of infusion time is safely reached, cohorts of 3-6 patients receive escalating doses of KRN5500 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with KRN5500 at the recommended phase II dose. |
相関研究
他の名前：
Given IV
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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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Maximally tolerated dose (MTD) and dose limiting toxicities (DLTs) of KRN5500, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
時間枠：Up to 21 days
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Up to 21 days
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Grade 2 or greater toxic effects, based on the NCI CTC v2.0
時間枠：Up to 1 month after last course of study treatment
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Up to 1 month after last course of study treatment
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Plasma concentration-time levels of KRN5500 as determined by reversed-phase high-performance liquid chromatography with electrospray ionization mass spectrometric detection
時間枠：Up to 21 days
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Analyzed by noncompartmental methods and/or nonlinear least squares regression using WinNonlin (Scientific Consulting, Inc.).
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Up to 21 days
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Response to KRN5500 by fluorothymidine-positron emission tomography (FLT-PET) scanning at the MTD in patients with measurable disease
時間枠：Up to 5 years
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Up to 5 years
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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抗腫瘍活性
時間枠：5年まで
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5年まで
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Pharmacodynamic relationships for the pharmacological effect of the drug upon surrogate markers of activity and host toxicity
時間枠：Up to 21 days
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Up to 21 days
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Comparison among the toxicity profiles between the 1 hr i.v. infusion and 72 hr continuous i.v. infusion administration schedules
時間枠：Up to 1 month after last course of study treatment
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Up to 1 month after last course of study treatment
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協力者と研究者
捜査官
- 主任研究者：Joseph Eder、Dana-Farber Cancer Institute
研究記録日
主要日程の研究
研究開始
一次修了 (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
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