Prior Axitinib as a Determinant of Outcome of Renal Surgery (PADRES)
"PADRES" (Prior Axitinib as a Determinant of Outcome of REnal Surgery)
This is a single arm phase II study of axitinib in patients with clear cell renal cell carcinoma (RCC) with strong indications for partial nephrectomy (PN) for whom PN is not currently possible due to anatomic considerations and residual renal function concerns. Evaluation of tumor downsizing will be performed including changes of tumor complexity by nephrometry score. A total of 50 participants will be enrolled.
It is hypothesized that pretreatment with axitinib will be safe and improve the feasibility of complex nephron sparing surgery in select patients with localized clear cell RCC and imperative indications for partial nephrectomy.
調査の概要
詳細な説明
The primary objective of the study is to prospectively assess utility of axitinib in facilitation of partial nephrectomy where partial nephrectomy was not thought to be safe/possible in the setting of imperative indication for complex renal masses in renal cell cancer.
Secondary objectives: To determine the safety, tumor diameter (per RECIST v1.1) volume change, surgical morbidity and renal functional outcomes following neoadjuvant axitinib for RCC.
Anatomical/morphometric:
- tumor diameter/volume change,
- conversion of hilar to non-hilar tumors,
- reduction in RENAL morphometric score.
Functional Considerations:
- Requirement of acute dialysis
- Change in Glomerular Filtration Rate (GFR)
- Whether or not GFR crosses 30 threshold, or decline by GFR to >50% of baseline.
Safety indices:
- Incidence of Clavien >3 complications
- Avoidance of need for multiple blood transfusions
研究の種類
入学 (予想される)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前:William Brocklehurst
- 電話番号:8585345751
- メール:wbrocklehurst@ucsd.edu
研究場所
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California
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La Jolla、California、アメリカ、92093
- 募集
- UC San Diego Moores Cancer Center
-
コンタクト:
- Arlene Araneta
- 電話番号:8588226187
- メール:aaraneta@ucsd.edu
-
-
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:
- Localized clear cell renal carcinoma without evidence of distant metastases
Imperative indication for nephron sparing surgery
- Baseline chronic kidney disease (CKD) (stage 3, GFR <60 ml/min/1.73m2), or anatomically or functional solitary kidney (defined by renal scintigraphy of contralateral renal unit with <15% function) or bilateral synchronous disease); and
- RENAL score ≥10 or proximity to renal hilum (defined as <2 mm away from at least 2 renal hilar vessels-the main artery/vein or first order branches); and
- Radical nephrectomy would lead to severe CKD (stage 3b, GFR <45 ml/min/1.73m2).
- Male or female, age ≥ 18 years
- Karnofsky performance status ≥ 70.
Adequate organ function as defined by:
- Absolute neutrophil count (ANC) ≥1,000/μL
- Platelets ≥100,000/μL
- Hemoglobin ≥9.0 g/dL
- Serum calcium ≤12.0 mg/dL
- Serum creatinine ≤1.5 x upper limit of normal (ULN)
- Total serum bilirubin ≤1.5 x ULN
- SGOT≤2.5 x ULN and serum glutamic pyruvic transaminase (SGPT) ≤2.5x ULN
- Signed informed consent and willingness/ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
Exclusion Criteria:
- Presence of metastatic disease on radiographic imaging.
- Elective indication for nephron sparing surgery
- Non-clear cell histology
- Prior systemic treatment of any kind or radiotherapy for RCC
- NCI CTCAE Version 5.0 grade 3 hemorrhage within 4 weeks of starting the study treatment
- Ongoing cardiac dysrhythmias of NCI CTCAE Version 5.0 grade ≥2. Controlled atrial fibrillation is permitted. Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG >480 msec.
- Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal,or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
- Uncontrolled hypertension (HTN): systolic blood pressure ≥150 or diastolic blood pressure ≥ 100 mmHg or both despite appropriate therapy.
- HTN with need for greater than three anti-hypertensive agents at baseline. Drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each formulation.
- New York Heart Association (NYHA) class III or greater congestive heart failure (CHF)
- Uncontrolled hyper- or hypothyroidism.
- Subjects with arterial thrombotic events in the prior 12 months (axitinib has never been studied in this population)
- Subjects who have had venous thrombotic events in the prior 6 months (axitinib has never been studied in this population)
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:Axitinib Oral Tablet [Inlyta]
Axitinib 5 mg PO BID for 8-10 weeks
|
Axitinib 5 milligrams (mg) administered orally (po) twice daily (BID) for 8 weeks (with titration to 7 mg BID as tolerated at 4 weeks)
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 |
メジャーの説明 |
時間枠 |
---|---|---|
Percent reduction of longest diameter of tumor in millimeters
時間枠:90 days
|
90 days
|
|
Objective Tumor Response Rate (by RECIST criteria)
時間枠:90 days
|
Percentage of patients achieving partial response (reduction in tumor diameter by at least 30% of maximum diameter) as defined by RECIST criteria
|
90 days
|
Effect on tumor morphometry, as measured by RENAL score [(R)adius, (E)xophytic/endophytic components, (N)earness to the collecting system or sinus, (A)neterior/posterior, and (L)ocation relative to polar lines]
時間枠:90 days
|
The RENAL nephrometry score quantifies tumor size and location relative to the major blood vessel and collecting system supply of the kidney according to 5 domains (tumor radius, exophytic/endophytic appearance, proximity to urinary collecting system, anterior/posterior location, and location with respect to renal poles).
Four of these domains have a score of 1-3, with 3 indicating a more complex score within the domain.
The total score is the sum of all of the domains (total minimum score being 4 and the maximum score being 12, and with more complex tumors having a higher score).
The study will record effect of the medication on tumor complexity as measured by total RENAL nephrometry score.
|
90 days
|
Feasibility of partial nephrectomy surgery
時間枠:90 days
|
Percentage of Successful partial nephrectomy perfomed (as opposed to radical nephrectomy) with negative surgical margins determined by pathological assessment of resection margins.
|
90 days
|
協力者と研究者
捜査官
- スタディチェア:Ithaar H Derweesh, MD、UC San Diego Moores Cancer Center
- 主任研究者:Ithaar H Derweesh, MD、UC San Diego Moores Cancer Center
- 主任研究者:Brian I Rini, MD、The Cleveland Clinic
- 主任研究者:Steven C Campbell, MD, PhD、The Cleveland Clinic
出版物と役立つリンク
一般刊行物
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研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
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 (実際)
学習記録の更新
投稿された最後の更新 (実際)
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
- 161197
- WI209751 (その他の助成金/資金番号:Pfizer Inc)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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明細胞腎細胞がんの臨床試験
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