Irinotecan, Oxaliplatin, and Capecitabine in Treating Patients With Unresectable Solid Tumors
A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors
調査の概要
詳細な説明
OBJECTIVES:
I. To define the maximally tolerated dose of the combination of CPT-11 (irinotecan hydrochloride), oxaliplatin, and capecitabine in three different populations, based on UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype (6/6, 6/7, and 7/7).
II. To identify any activity of this treatment combination in patients with metastatic cancer.
III. To examine the differences in the toxicity profile, especially pertaining to hematologic and gastrointestinal (GI), and the maximally tolerated dose of the combination of CPT-11, oxaliplatin and capecitabine with respect to the UGT1A1 haplotypes.
IV. Examine the effect of the UGT1A1 genotype on the pharmacokinetics of CPT-11 and its metabolites.
OUTLINE: This is a dose-escalation study. Patients are stratified according to UGT1A1 genotype (6/6 vs 6/7 [closed to accrual as of 8/24/06] vs 7/7).
Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (QD) on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride, oxaliplatin, and capecitabine 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, an additional 6-10 patients (for a total of 12 patients) receive treatment at that dose.
After completion of study treatment, patients are followed up at 3 months.
PROJECTED ACCRUAL: A total of 54-84 patients (12-22 for stratum I, 18-28 for stratum II [closed to accrual as of 8/24/06], and 24-34 for stratum III) will be accrued for this study within approximately 4.4 years.
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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Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
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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:
Histologically confirmed solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy
- Unresectable disease
- Willing to provide biologic specimens to determine UGT1A1 genotype
No CNS metastases
- Prior CNS metastases allowed provided patient was treated with surgery and/or radiotherapy and is stable for more than 8 weeks
- Performance status - ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9.0 g/dL
- Bilirubin no greater than upper limit of normal (ULN) for patients with 6/6 UGT1A1 genotype (1.5 times ULN for patients with 6/7 [closed to accrual as of 8/24/06] or 7/7 UGT1A1 genotype)
- AST no greater than 3 times ULN (5 times ULN if there is liver involvement)
- Creatinine no greater than 1.5 times ULN
- No New York Heart Association class III or IV heart disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior allergy to platinum compounds, irinotecan, or to antiemetics or antidiarrheals appropriate for administration with study therapy
- No uncontrolled infection
- No seizure disorder
- No peripheral neuropathy grade 2 or greater
- More than 4 weeks since prior biologic therapy
- More than 4 weeks since prior immunotherapy
- No concurrent immunotherapy
- No concurrent prophylactic colony-stimulating factor therapy
- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
- No other concurrent chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to more than 25% of the bone marrow
- No concurrent radiotherapy
- See Disease Characteristics
- No other concurrent investigational therapy
- No concurrent sorivudine, brivudine, lamivudine, or stavudine
- No concurrent enrollment in any other study involving a pharmacologic agent for symptom control or therapeutic intent
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 |
---|---|
実験的:Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15.
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
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相関研究
与えられた IV
他の名前:
相関研究
他の名前:
与えられたPO
他の名前:
与えられた IV
他の名前:
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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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MTD defined as one dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) assessed using NCI CTCAE v3.0
時間枠:3 weeks
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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 |
---|---|---|
治療に関連した毒性が現れるまでの時間
時間枠:最長3ヶ月
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わかりやすくまとめていきます。
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最長3ヶ月
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治療に関連したグレード3以上の毒性が発現するまでの時間
時間枠:最長3ヶ月
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わかりやすくまとめていきます。
|
最長3ヶ月
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進歩するまでの時間
時間枠:最長3ヶ月
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わかりやすくまとめていきます。
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最長3ヶ月
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治療失敗までの時間
時間枠:登録から進行、許容できない毒性、または患者による参加継続の拒否の記録まで、最長 3 か月間評価されます
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わかりやすくまとめていきます。
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登録から進行、許容できない毒性、または患者による参加継続の拒否の記録まで、最長 3 か月間評価されます
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Incidence of UTG1A1*28 polymorphism
時間枠:Up to 3 months
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The overall incidence of UTG1A1*28 polymorphism will be estimated and summarized in this patient population.
In addition, the incidence of this polymorphism will be explored in relation to tumor type.
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Up to 3 months
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Adverse events profile assessed using NCI CTCAE v3.0
時間枠:Up to 3 months
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The number and severity of all adverse events (overall, by dose level, and by tumor group) will be tabulated and summarized for the three patient groups.
The grade 3+ adverse events will also be described and summarized in a similar fashion.
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Up to 3 months
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Toxicity profile assessed using NCI CTCAE v3.0
時間枠:Up to 3 months
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Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized in each of the two groups.
Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
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Up to 3 months
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Response profile using RECIST criteria
時間枠:Up to 3 months
|
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as table and progressive disease in the two patient populations (overall and by tumor group).
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Up to 3 months
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Time until hematologic nadirs (WBC, ANC, platelets)
時間枠:Up to 3 months
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Will be summarized descriptively.
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Up to 3 months
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協力者と研究者
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
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-2012-01444
- MC0311
- NCI-6240
- CDR0000344367
- MAYO-MC0311
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