Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
A Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
調査の概要
詳細な説明
This is an open label, multiple site, pilot study. Hypothesis: Treatment with Burixafor hydrobromide will effectively mobilize metastatic prostate cancer (PCa) cells (i.e. disseminated tumor cells; DTCs) into the blood from the bone marrow. In preclinical models, these bone marrow niche engaged cells are more resistant to therapy as compared to soft tissue sites.
It has been demonstrated that prostate cancer cells have been mobilized out of the bone marrow of mice utilizing an anti-CXCR4 strategy; making them more susceptible to chemotherapy. Currently, the anti-CXCR4 agent plerixafor is FDA approved to be given for up to 4 consecutive days in order to mobilize hematopoietic stem cells (HSCs).
Burixafor hydrobromide is a potent anti-CXCR4 agent that is in clinical trials. Burixafor hydrobromide, alone or in combination with G-CSF, is currently in Phase II testing for use as a hematopoetic stem cell (HSC) mobilization agent. When Burixafor hydrobromide is given intravenously (IV) alone at a dose of 3.14 mg/kg it has been shown to result in a 7.8 fold mean increase in peripheral blood CD34+ (a HSC marker) cells 6-hours post-infusion.
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
-
-
Maryland
-
Baltimore、Maryland、アメリカ、21287
- Johns Hopkins University
-
-
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:
- Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study
- Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
- Male aged 18 years and above
- Eastern cooperative group (ECOG) performance status ≤2
- Documented histologically confirmed adenocarcinoma of the prostate
- Metastatic prostate cancer to the bone as documented by positive bone scan imaging
- Patient must be eligible for chemotherapy with docetaxel
- Patient must have evidence of castrate resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a castrate serum testosterone level (i.e. ≤ 50 mg/dL).
Exclusion Criteria:
- Have known allergies, hypersensitivity, or intolerance to docetaxel or dexamethasone or their excipients
- Prior pelvic radiation (e.g. external beam, brachytherapy, etc) that, in the opinion of the investigator, may lead to decreased bone marrow cellularity in a marrow sample obtained from a pelvic bone marrow biopsy
Ongoing systemic therapy (other than a GnRH agonist/antagonist) for prostate cancer including, but not limited to:
- CYP-17 inhibitors (e.g. ketoconazole, abiraterone)
- Antiandrogens (e.g. bicalutamide, nilutamide)
- Second generation antiandrogens (e.g. enzalutamide)
- Immunotherapy (e.g. sipuleucel-T, ipilimumab)
- Chemotherapy (e.g. docetaxel, cabazitaxel)
- Prior radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153, etc) within the past year
- Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
- Active infection or other medical condition that would make corticosteroids (i.e. dexamethasone) use contraindicated
- Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg) Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
- Severe hepatic impairment (Child-Pugh Class C)
- History of pituitary or adrenal dysfunction (note: the use of daily steroids does not exclude someone from participating in this study)
- Have poorly controlled diabetes (HgB A1C ≥ 8%)
- Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
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:非ランダム化
- 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 |
|---|---|
|
アクティブコンパレータ:burixafor hydrobromide
Four daily doses of burixafor hydrobromide alone
|
Investigators will determine the kinetics of PCa cell release into the blood with four daily dosages of Burixafor hydrobromide alone or in combination with G-CSF
|
|
アクティブコンパレータ:G-CSF
G-CSF will be given as a daily subcutaneous (SC) injection beginning 4 days prior to Burixafor hydrobromide and continuing through the 4 days of Burixafor hydrobromide treatment
|
G-CSF will be given as a daily subcutaneous (SC) injection beginning 4 days prior to Burixafor hydrobromide and continuing through the 4 days of Burixafor hydrobromide treatment
他の名前:
|
|
実験的:Docetaxel
Investigators will administer a single 75 mg/m2 IV dose of docetaxel. Twenty-one days later investigators will re-treat enrolled men with the optimal mobilization strategy + docetaxel IV. The second dose of docetaxel being given in combination with the optimal mobilization strategy will be chosen according to a standard 3+3 dose escalation schema, in which the dose of bruixafor +/- G-CSF will be held constant and the dose of docetaxel will escalate between three dose-levels: 1) docetaxel 30 mg/m2 IV, 2) docetaxel 60 mg/m2 IV, and 3) docetaxel 75 mg/m2 |
Investigators will administer a single 75 mg/m2 IV dose of docetaxel.
Twenty-one days later investigators will re-treat enrolled men with the optimal mobilization strategy + docetaxel IV.
The second dose of docetaxel being given in combination with the optimal mobilization strategy will be chosen according to a standard 3+3 dose escalation schema, in which the dose of bruixafor +/- G-CSF will be held constant and the dose of docetaxel will escalate between three dose-levels: 1) docetaxel 30 mg/m2 IV, 2) docetaxel 60 mg/m2 IV, and 3) docetaxel 75 mg/m2
|
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 |
|---|---|---|
|
Mobilization of DTCs from bone marrow
時間枠:2 years
|
Measure the number of CTCs in the peripheral blood.
|
2 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time
時間枠:2 years
|
This will be reported as number of tumor cells/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.
|
2 years
|
|
Kinetics of hematopoietic stem cell (HSC) mobilization by quantifying the number of circulating HSCs per milliliter of blood over time
時間枠:2 years
|
This will be reported as number of HSC/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.
|
2 years
|
|
PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel
時間枠:2 years
|
2 years
|
|
|
Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel
時間枠:2 years
|
Safety will be evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events
|
2 years
|
|
Exploratory biomarker Assessment on CTCs/DTCs
時間枠:2 years
|
Examples of these may include, but are not limited to: assessment of cell cycle kinetics, apoptosis, PTEN status, MYC alterations, whole genome, whole exome, and transcriptome analysis
|
2 years
|
協力者と研究者
捜査官
- 主任研究者:Kenneth Pienta, MD、Johns Hopkins 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 (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 (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
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。
前立腺がんの臨床試験
-
Novartis Pharmaceuticals終了しましたメラノーマ | 高度なEGFR変異体非小さな細胞肺cancer(NSCLC) | KRAS G12変異NSCLC | 食道扁平上皮がん(SCC) | ヘッド/ネックSCC | 進行した胃腸間質腫瘍(GIST) | 進行したNRAS/BRAFT WT皮膚黒色腫アメリカ, 台湾, オランダ, カナダ, スペイン, シンガポール, イタリア, 日本, 韓国
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); Highlight Therapeutics積極的、募集していない平滑筋肉腫 | 悪性末梢神経鞘腫瘍 | 滑膜肉腫 | 未分化多形肉腫 | 骨の未分化高悪性度多形肉腫 | 粘液線維肉腫 | II期の体幹および四肢の軟部肉腫 AJCC v8 | III期の体幹および四肢の軟部肉腫 AJCC v8 | IIIA 期の体幹および四肢の軟部肉腫 AJCC v8 | IIIB 期の体幹および四肢の軟部肉腫 AJCC v8 | 切除可能な軟部肉腫 | 多形性横紋筋肉腫 | 切除可能な脱分化型脂肪肉腫 | 切除可能な未分化多形肉腫 | 軟部組織線維肉腫 | 紡錘細胞肉腫 | ステージ I 後腹膜肉腫 AJCC (American Joint Committee on Cancer) v8 | 体幹および四肢の I 期軟部肉腫 AJCC v8 | ステージ... およびその他の条件アメリカ