Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer
A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma
RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to kidney cancer cells. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving denileukin diftitox together with interleukin-2 may kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects of denileukin diftitox and interleukin-2 in treating patients with metastatic kidney cancer.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Determine the toxic effects of denileukin diftitox and high-dose interleukin-2 in patients with metastatic renal cell cancer.
Secondary
- Perform transforming growth factor (TGF)-beta promoter and TGF-beta receptor genotyping to search for variants that may be associated with tumor response to therapy.
- Determine the overall response rate (partial and complete) in patients treated with this regimen.
- Determine the time to progression in patients treated with this regimen.
OUTLINE: This is a randomized, pilot study.
The first 3 patients enrolled in the study receive high-dose interleukin-2 (IL-2) IV over 15 minutes, 3 times daily, on days 1-5 and 15-19 and denileukin diftitox IV over 15-60 minutes once daily on days 8-10. If no dose-limiting toxicity occurs after receiving denileukin diftitox, subsequent patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes once daily on days -4 to -2 and high-dose IL-2 IV over 15 minutes, 3 times daily, on days 1-5 and 15-19.
- Arm II: Patients receive high-dose IL-2 as in arm I and denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes at a higher dose once daily on days 8-10.
All patients may receive additional treatment with IL-2 alone in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for at least 4 years.
PROJECTED ACCRUAL: A total of 13 patients will be accrued for this study.
研究の種類
入学 (実際)
段階
- 初期フェーズ 1
連絡先と場所
研究場所
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Illinois
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Chicago、Illinois、アメリカ、60611-3013
- Robert H. Lurie Comprehensive Cancer Center at Northwestern University
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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
DISEASE CHARACTERISTICS:
Documented histologically confirmed metastatic renal cell carcinoma
- Clear cell histology
Disease must be measurable as defined by lesions that can be accurately measured in at least one dimension with longest diameter > 20 mm using conventional techniques or > 10 mm with spiral CT scan
- Must have at least one measurable lesion
- If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology
- Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes)
The following are considered nonmeasurable lesions:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural/pericardial effusion
- Inflammatory breast disease
- Lymphangitis cutis/pulmonis
- Cystic lesions
- Abdominal masses not confirmed and followed by imaging techniques
- No CNS metastases
PATIENT CHARACTERISTICS:
- ECOG performance status < 2
- Life expectancy of at least 4 months
- Serum creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
- Total bilirubin normal
- Platelets > 100,000/mm³
- WBC > 3,500/mm³
- No evidence of congestive heart failure
- No symptoms of coronary artery disease
- No serious cardiac arrhythmias
- A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment if any cardiac symptoms are present (patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study)
Adequate pulmonary reserve
Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment
- FEV_1 > 2.0 liters of > 75% predicted for height and age
- Patients unable to perform PFTs will be excluded
- Women who are pregnant or lactating are not eligible
- Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study
- Negative pregnancy test
- No known HIV-positive patients
- No evidence of active infection requiring antibiotic therapy
- Must not have a contraindication to treatment with pressor agents
- Must not have any significant medical disease that, in the opinion of the investigator, may interfere with completion of the study
- No history of another malignancy within the past 5 years other than basal cell skin cancer
PRIOR CONCURRENT THERAPY:
- Recovered from all toxic effects of prior therapy
- Must not currently receive chronic medication for asthma
- No prior interleukin-2 (IL-2) therapy
- No prior organ allografts
- No systemic corticosteroids in the 4 weeks prior to treatment
- No concurrent systemic steroids
- No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of study treatment
- No concurrent radiotherapy, chemotherapy, or other immunotherapy
- No previous investigational agent within 4 weeks prior to the start of study treatment
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: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 |
---|---|
実験的:A
6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
|
The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment.
IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5).
A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19).
This is one complete cycle (days 1-19) of IL-2 treatment
他の名前:
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
他の名前:
|
実験的:B
9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course
|
The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment.
IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5).
A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19).
This is one complete cycle (days 1-19) of IL-2 treatment
他の名前:
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
他の名前:
|
実験的:C
9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
|
The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment.
IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5).
A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19).
This is one complete cycle (days 1-19) of IL-2 treatment
他の名前:
Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.
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 |
---|---|---|
The primary objective is to assess for toxicity
時間枠:After each cycle of therapy and 30 days after the last treatment.
|
To assess the toxicity
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After each cycle of therapy and 30 days after the last treatment.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
The secondary objectives are to investigate differences in peak and duration of the expansion of CD4+, CD8+, CD4+CD 25+ and CD56+(dim and bright)CD25+ cells
時間枠:Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks.
|
To investigate differences in peak and duration.
|
Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks.
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To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels
時間枠:Cohort 1: Denileukin diftitox dose of 6μg/kg/ Days 1, 2, 3, 4, and 5. Cohort 2 Denileukin diftitox dose of 9μg/kg given 4, 3, 2, and 1 days prior to 1st day of each cycle. Cohort 3: Denileukin diftitox dose of 9μg/kg given days 8 and 9.
|
To investigate the effects of denileukin diftitox
|
Cohort 1: Denileukin diftitox dose of 6μg/kg/ Days 1, 2, 3, 4, and 5. Cohort 2 Denileukin diftitox dose of 9μg/kg given 4, 3, 2, and 1 days prior to 1st day of each cycle. Cohort 3: Denileukin diftitox dose of 9μg/kg given days 8 and 9.
|
To perform TGF-beta promoter and TGF-beta receptor genotyping prior to the start of treatment to search for variants that may be associated with tumor response to therapy.
時間枠:Cohort 1: Plasma TGF-beta levels to be given on day. Cohort 2: plasma TGF-beta levels to be given at day 1. Cohort 3: plasma TGF-beta levels given on days 1 through 5.
|
To perform TGF-beta promoter and TGF-beta receptor genotyping
|
Cohort 1: Plasma TGF-beta levels to be given on day. Cohort 2: plasma TGF-beta levels to be given at day 1. Cohort 3: plasma TGF-beta levels given on days 1 through 5.
|
Overall response rate and time to progression
時間枠:CT scans and other pertinent studies will be performed at week 10 to assess response.
|
Overall response rate will be assessed.
|
CT scans and other pertinent studies will be performed at week 10 to assess response.
|
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)
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
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
- NU 04U1
- P30CA060553 (米国 NIH グラント/契約)
- NU-04U1
- STU00006770 (その他の識別子:Northwestern University IRB)
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。
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