前立腺癌患者における 177Lu 放射性標識モノクローナル抗体 HuJ591 (177Lu-J591) およびケトコナゾール
177Lu 放射性標識モノクローナル抗体 HuJ591 (177Lu-J591) とケトコナゾールの無作為化第 2 相試験は、局所療法後に生化学的に再発した高リスクの去勢前立腺がん患者を対象としています。
The purpose of this study is to test the effectiveness of the experimental drug, 177Lu-J591 in combination with ketoconazole and hydrocortisone against prostate cancer.
調査の概要
詳細な説明
This research is being done because the standard treatments for prostate cancer that has returned (PSA is elevated) after surgery and/or radiation and progressed on initial hormonal therapy are not curative. Existing treatments, such as the ketoconazole used as part of this study may decrease PSA temporarily, but unfortunately the cancer continues to grow. This experimental drug is designed to seek out all of the prostate cancer cells and to deliver a lethal dose of radiation to the areas of cancer, but not to normal areas. Some of the normal organs (liver, kidney and bone marrow) do receive some radiation dose that is within the acceptable limits.
The experimental drug in this study includes an antibody (abbreviated: mAb) called "J591". It is a protein molecule which can bind to a specific site on a prostate cancer cell. A very energetic radioactive (an unstable atom) metal called 177Lutetium (abbreviated: 177Lu) is attached to the J591 antibody. The fully assembled drug is called "177Lu-J591". The study will assess the potential of the energy given off by the radioactive compound to kill cancer cell. This study may also involve the use of 111Indium (abbreviated 111In). This is also an energetic radioactive particle, but does not generally give off enough energy to kill cancer cells, but allows researchers to take pictures. This radioactive particle is also attached to the J591 antibody (called 111In-J591) and will serve as a placebo (treatment with no active medicine).
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
California
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Los Angeles、California、アメリカ、90048
- Cedars Sinai
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Los Angeles、California、アメリカ、90089
- USC/Norris Comprehensive cancer center
-
-
District of Columbia
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Washington D.C.、District of Columbia、アメリカ、20007
- Georgetown University Medical Center
-
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Indiana
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Indianapolis、Indiana、アメリカ、46202
- Indiana University Melvin and Bren Simon Cancer Center
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-
Iowa
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Iowa City、Iowa、アメリカ、52242
- University of Iowa Hospitals and Clinics
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Kansas
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Westwood、Kansas、アメリカ、66205
- The University of Kansas Cancer Center
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-
Nebraska
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Omaha、Nebraska、アメリカ、68130
- XCancer Omaha
-
-
New York
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New York、New York、アメリカ、10021
- Weill Cornell Medical College
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- UPMC Hillman Cancer Center
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-
Utah
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Salt Lake City、Utah、アメリカ、84108
- University of Utah
-
-
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 or cytologically confirmed adenocarcinoma of the prostate previously treated with surgery and/or radiotherapy.
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Biochemical progression (rising PSA) after medical or surgical castration
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High risk of systemic progression defined as:
- Rising PSA as defined above and either:
- Absolute PSA > 20 ng/mL AND/OR
- PSA doubling time < 8 months
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No evidence of local recurrence or distant metastases
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Age >18 years.
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Serum testosterone < 50 ng/ml
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Patients capable of fathering children must agree to use an effective method of contraception for the duration of the trial.
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Subjects on bisphosphonate therapy must be on a stable dose and must have started therapy > 4 weeks prior to protocol therapy.
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Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
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Use of red blood cell or platelet transfusions within 4 weeks of treatment
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Use of hematopoietic growth factors within 4 weeks of treatment
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Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment
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Prior radiation therapy encompassing >25% of skeleton (see Appendix C)
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Prior treatment with 89Strontium or 153Samarium containing compounds (e.g. Metastron®, Quadramet®)
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Platelet count <150,000/mm3 or known primary qualitative platelet disorder
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Absolute neutrophil count (ANC) <2,000/mm3
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Hematocrit <30 percent and Hemoglobin < 10 g/dL
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Abnormal coagulation profile (PT or INR, PTT > 1.3x ULN) unless on therapeutic anticoagulation - see concomitant meds section
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Serum creatinine >2.5 mg/dL
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AST (SGOT) >2x ULN
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Bilirubin (total) >1.5x ULN; subjects with Gilbert's syndrome will be allowed if direct bilirubin is within institutional normal limits
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Active serious infection
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Active angina pectoris or NY Heart Association Class III-IV
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ECOG Performance Status > 2
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Life expectancy <12 months
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History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry
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Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
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Prior investigational therapy (medications or devices) within 4 weeks of treatment. Furthermore, other investigational therapy is not permitted during the treatment phase.
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Prior use of ketoconazole for the purposes of prostate cancer therapy for greater than 1 month
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Known history of HIV. The effects of J591 are unknown in this population. Furthermore, ketoconazole has many well-described drug-drug interactions which could affect antiviral therapy. If necessary, this population will be studied separately.
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Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
- Known history of known myelodysplastic syndrome
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Adrenal hormone inhibitors (other than ketoconazole) within 4 weeks prior to study enrollment
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Finasteride (Propecia® or Proscar®) or dutasteride (Avodart®) within 4 weeks of enrollment
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Patients on corticosteroids prior to enrollment must have either discontinued and shown biochemical progression or have biochemical progression on a stable dose
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：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：1. 177Lu-J591 + Ketoconazole
Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 177Lu-J591 Infusion, continue ketoconazole and hydrocortisone |
177Lu-J591 70 mCi/m2 on day 29 (+/- 2 days) of treatment
他の名前：
Ketoconazole at a dose of 400 mg (two 200 mg tabs) to be taken orally (preferably on an empty stomach) three times per day (total daily dose of 1200 mg)
他の名前：
Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg)
他の名前：
|
|
プラセボコンパレーター：2. 111In-J591 + Ketoconazole
Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 111In-J591 (placebo) Infusion, continue ketoconazole and hydrocortisone |
Ketoconazole at a dose of 400 mg (two 200 mg tabs) to be taken orally (preferably on an empty stomach) three times per day (total daily dose of 1200 mg)
他の名前：
Hydrocortisone at a dose of 20 mg orally each morning, 10 mg orally each evening (total daily dose of 30 mg)
他の名前：
111In-J591 at a dose of 5 mCi on day 29 (+/- 2 days) of treatment
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 |
|---|---|---|
|
Proportion of Participants Free of Radiographically Evident Metastases From Baseline to 18 Months After Study Drug Administration
時間枠：Baseline and 18 months after study drug administration
|
Subjects will perform a CT and/or MRI scan of the abdomen and pelvis, chest x-ray or CT scan of the chest and bone scan to determine the proportion of participants free of radiographically evident metastases from baseline to 18 months after study drug administration. |
Baseline and 18 months after study drug administration
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in PSA Response Rate
時間枠：Collected at screening, V2, V3, V5, V9 then every 4 weeks till PSA progression or end of study at approximately 100 months
|
PSA response will be determined by comparing the PSA levels after therapy to the baseline and pre-treatment PSA via blood specimens |
Collected at screening, V2, V3, V5, V9 then every 4 weeks till PSA progression or end of study at approximately 100 months
|
協力者と研究者
捜査官
- 主任研究者：Scott T Tagawa, M.D.、Weill Medical College of Cornell University
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (推定)
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 (推定)
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
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 0810010067
- J591+Ketoconazole (その他の識別子：Weill Cornell Medicine)
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
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