Study of Sunitinib Malate in Patients With Newly Diagnosed Prostate Cancer Prior to Prostatectomy
2014年7月31日 更新者：Duke University
Investigator-Initiated Pilot Study of Sunitinib Malate in Patients With Newly Diagnosed Prostate Cancer Prior to Prostatectomy
The purpose of this study is to look at blood and tissue samples for changes following the use of Sunitinib malate.
Additionally, we would like to find out if the drug, Sunitinib malate, is safe and works in men with prostate cancer.
Sunitinib malate , also known as Sutent, is approved by the U.S. Food and Drug Administration (FDA), for treatment of tumors of intestines and kidney but it is being tested in research studies for use in men with prostate cancer.
調査の概要
詳細な説明
Eligible patients will be treated with 50 mg once daily for four weeks followed by one to two weeks off treatment prior to undergoing radical prostatectomy.
Patients with palpable disease (cT2-3) and patients with 3 or more positive prostatic biopsies from one lobe may undergo an additional study of IFP monitoring before treatment and during week 4 of study treatment.
Safety and tolerability of Sunitinib malate therapy at this dose and schedule in this patient population will be assessed.
Extensive correlative science evaluations, including assessment of physiologic, cellular, molecular and genetic changes during treatment with Sunitinib malate, will be performed
研究の種類
介入
入学 (実際)
30
段階
- フェーズ2
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
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North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke University Medical Center
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Texas
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Houston、Texas、アメリカ、77030
- MD Anderson, University of Texas
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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
18年歳以上 (大人、高齢者)
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
男
説明
Inclusion Criteria:
- Histologic evidence of adenocarcinoma of the prostate deemed candidates for curative RRP
- Intermediate or high risk, clinically localized disease
- Adequate organ function
- Patients must be surgically sterile or must agree to use effective contraception during the period of therapy
- Select imaging to rule out metastasis will be done as clinically indicated
- Signed and date informed consent document
Exclusion Criteria:
- Prior treatment for prostate cancer
- Major surgery or radiation therapy within 4 weeks of starting the study treatment
- NCI CTCAE grade 3 hemorrhage within 4 weeks of starting therapy
- History of or known metastatic prostate cancer
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
- Ongoing cardiac dysrhythmias of NCI CTCAE grade 2 or greater
- QTc interval > 500 msec on baseline EKG
- Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy).
- Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
- Known active infection
- Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
- 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.
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 |
|---|---|
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実験的：Sunitinib Malate
Sunitinib Malate 50mg capsule by mouth once daily for 4 weeks
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Sunitinib Malate 50mg capsule by mouth once daily for 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 |
|---|---|---|
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Change in Apoptotic Indices Before and After Treatment
時間枠：Baseline and 4 weeks
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Pathologic changes will be described using immuno-histochemical techniques (assessment of apoptotic/proliferative indices and microvessel density (MVD)) using paraffin-embedded samples and freshly cut slides from the block which are deparaffinized and rehydrated through graded alcohol, where applicable.
Antigen retrieval will be accomplished by microwaving in citrate buffer from 5 to 7 minutes for the Ki-67 and MVD analysis.
Mean difference in %apoptosis (measured as %TUNEL positive cells per high powered field) between pre and post treatment will be reported.
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Baseline and 4 weeks
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Change in Proliferation Indices Before and After Treatment
時間枠：Baseline and 4 weeks
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Pathologic changes will be described using immuno-histochemical techniques (assessment of apoptotic/proliferative indices and microvessel density (MVD)) using paraffin-embedded samples and freshly cut slides from the block which are deparaffinized and rehydrated through graded alcohol, where applicable.
Antigen retrieval will be accomplished by microwaving in citrate buffer from 5 to 7 minutes for the Ki-67 and MVD analysis.
Mean difference in %proliferation (Ki67 positive nuclei out of total nuclei) between pre and post treatment will be reported.
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Baseline and 4 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 |
|---|---|---|
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Number of Patients Experiencing Grade ≥4 Hematologic or Grade ≥3 Non-hematologic Toxicity
時間枠：4 years
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Adverse events were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were converted to version 4.0 for the purposes of ClinicalTrials.gov
reporting.
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4 years
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Change in Pathologic (Microvessel Density).
時間枠：Baseline and 4 weeks
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Pathologic changes will be described using immuno-histochemical techniques (assessment of microvessel density (MVD)) using paraffin-embedded samples and freshly cut slides from the block which are deparaffinized and rehydrated through graded alcohol, where applicable.
Antigen retrieval will be accomplished by microwaving in citrate buffer from 5 to 7 minutes for the MVD analysis.
Results are reported as the difference in pre and post MVD.
Units for MVD are number of CD31 cells per high powered field.
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Baseline and 4 weeks
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Change in Systemic Parameters Before and After Sunitinib Malate Treatment.
時間枠：Baseline and 4 weeks
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We evaluated candidate biomarkers of this pathway to predict for pharmacodynamic response to Sunitinib malate.
In addition, a 7 ml plasma sample was collected at baseline and again at 4 weeks on all patients to assess possible biomarkers of response.
Reported is the mean percent change in plasma concentration for each marker between 4 weeks and baseline.
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Baseline and 4 weeks
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Protein Levels and Activation Status of PDGFR in Prostate Cancer Tissue.
時間枠：4 years
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We will perform immunohistochemistry staining on snap frozen specimens for endothelial and pericyte cell staining as previously described (42).
Frozen prostate tumor biopsies are sectioned at 6μm thickness and fixed with acetone for 10 minutes.
Endogenous peroxidase activity is quenched with 3% hydrogen peroxide for 15 min and then blocked with 5% normal serum.
The slides are incubated with the primary antibody (1;100) overnight at 4 C°, and washed with PBS.
Negative controls will be included by omission of the primary antibody.
Biotinylated donkey antimouse antibody (1:1000, v/v) will be applied for 30 min at room temperature, followed by application of ABC kit (Vector Lab, Inc., Burlingame, USA).
Slides are again washed in PBS and the color is developed by 5 min incubation with diaminobenzidine (DAB) solution.
Slides are then counterstained with hematoxylin.
Mean protein levels are presented.
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4 years
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Difference in Gene Expression Patterns Using Microarray Analysis
時間枠：4 years
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Microarray data of 21 specimens from men enrolled who have undergone a prostatectomy and study treatment were compared to data from 21 prostatectomy only specimens.
We used previously developed genomic signatures to measure the deregulation of oncogenic pathways built using Bayesian Probit models for 'metagene' factors from a singular value decomposition of top differentially expressed genes.
A Monte Carlo Markov Chain was used to generate the predicted probabilities of pathway activity in normalized samples.
We predicted the activity of these pathways, leading to the generation of probability measures that have previously reflected the state of pathway activity.
These probability scores are interpreted as gene expression values to describe pathway activity patterns.
A probability near 0 indicates a low chance of pathway activity; a probability near 1 indicates a higher likelihood of activity.
Differences (treatment - control) in mean probability for each pathway are reported.
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4 years
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Interstitial Fluid Pressure (IFP)
時間枠：4 years
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Measure Interstitial fluid pressure (IFP) pre-treatment and during treatment to indirectly measure the effect of Sunitinib malate on transcapillary transport and correlate with other biologic evidence of treatment effect.Eligible patients who sign consent will undergo a baseline transrectal ultrasound (TRUS)-guided measurement of tumor IFP.
Participants will then begin treatment with daily oral Sunitinib malate with biweekly monitoring for response and toxicity.
After 4 weeks of therapy, patients undergo a repeat TRUS and tumor IFP measurement.
Following a 1 to 2 week wash out period, patients undergo prostatectomy with pathologic tissue collection.
This will be performed as a means to evaluate whether Sunitinib malate has the ability to decrease tumor IFP, and whether this correlates with other tr
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4 years
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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。
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
2006年7月1日
一次修了 (実際)
2012年9月1日
研究の完了 (実際)
2013年9月1日
試験登録日
最初に提出
2008年5月4日
QC基準を満たした最初の提出物
2008年5月4日
最初の投稿 (見積もり)
2008年5月6日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年8月4日
QC基準を満たした最後の更新が送信されました
2014年7月31日
最終確認日
2014年5月1日
詳しくは
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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