PSMA-High: EBRT/ PSMA617/ ADT vs. EBRT/ ADT
高リスク限局性前立腺癌患者における外部照射（EBRT）と177Lu-PSMA-617および短期アンドロゲン抑制療法（ADT）の併用と、EBRTおよび長期ADTの併用を比較する第II相非盲検無作為化試験
This research is being done to find out if the study drug, 177Lu-PSMA-617, given before and during standard of care External Beam Radiation Therapy (EBRT) treatment, with a shorter course of Androgen Deprivation Therapy (ADT) (6 months) is (1) safe and effective compared to standard of care alone, and (2) can reduce the side effects caused by long-term (24 months) ADT in men with high risk localized prostate cancer.
調査の概要
詳細な説明
Men with high-risk localized prostate cancer include those with stage cT3a or Grade Group 4/5 or Prostate Specific Antigen (PSA) >20 ng/mL, and the proportional rate of high-risk disease has increased to 20% of newly diagnosed patients in the US. These patients are currently recommended treatment with a combination of definitive radiotherapy and long-term androgen deprivation therapy (NCCN category 1) or radical prostatectomy with pelvic lymph node dissection. Radiotherapy most often consists of external-beam radiotherapy (EBRT) in 28 to 45 daily fractions with 1.5 to 3 years of ADT. Multiple phase III studies have shown a benefit in survival with long-term ADT. However, given the toxicities of long-term ADT, including fatigue, mood changes, sexual dysfunction, osteopenia, weight gain, diabetes and cardiovascular disease, many patients are reluctant to complete long-term ADT. This leads to significant demand for investigation of lower-toxicity alternatives to long-term ADT for patients with high-risk localized prostate cancer.
The combination of 177Lu-PSMA-617 with definitive EBRT and 6 months ADT for high-risk prostate cancer has the potential to increase the cumulative absorbed dose to the prostate, involved nodes, and micrometastatic disease, as well as decrease toxicity and improve QoL compared with EBRT and long-term ADT. ADT has been shown to increase radiosensitivity and PSMA expression of prostate cancer; therefore 6 months of ADT was selected to optimize the combination therapy while avoiding toxicities associated with long-term ADT. There are significant unknowns with respect to absorbed dose and toxicities of this potential combination of 177Lu-PSMA-617 and EBRT. In addition, the relative efficacy compared to EBRT plus long-term ADT is unknown. The investigators therefore propose a phase II randomized study of dosimetry, safety, and efficacy of Lu-177-PSMA-617, EBRT, and short-term ADT (6 months) in comparison with EBRT and long-term ADT (24 months).
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Ryan Manuel
- 電話番号：410-955-4261
- メール：rmanuel5@jhmi.edu
研究連絡先のバックアップ
- 名前：Ana Kiess
- 電話番号：443-287-7528
- メール：akiess1@jhmi.edu
研究場所
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Maryland
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Baltimore、Maryland、アメリカ、21287
- 募集
- Johns Hopkins 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
Inclusion Criteria:
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Patient must have high-risk prostate cancer (HRPC) defined by presence of exactly one high-risk feature: cT3a OR Grade Group 4 or 5 OR PSA > 20 ng/mL.
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Histologic confirmation of adenocarcinoma of the prostate.
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Patient must have localized HRPC defined by conventional imaging (no N1 disease by CT or MRI). Patients with or without intra-pelvic nodal metastases by PSMA-PET may be included as long as not enlarged >10mm short axis by conventional CT size criteria.
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Patients must have PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL) with prostate tumor SUVmax > 10.
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Patient must qualify for definitive treatment of prostate cancer including EBRT as well as ADT (up to 45 days of prior ADT is allotted).
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Patient must be ≥ 18 years of age.
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Patient must have a life expectancy ≥ 24 months.
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Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
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Adequate bone marrow reserve and organ function as demonstrated by complete blood count and chemistry panel completed within the prior 6 weeks demonstrating:
- Platelet count of >100 x109/L
- White blood cell (WBC) count > 3,000/mL
- Neutrophil count of > 1,500/mL
- Hemoglobin ≥ 10 g/dL
- Estimated glomerular filtration rate (eGFR) > 50 mL/min based upon Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Due to safety concerns relating to renal clearance and toxicity of 177Lu-PSMA-617, patients with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only patients with non-obstructive pathology will be included in the study.
- Total bilirubin < 3 x ULN (except if confirmed history of Gilbert's disease)
- Serum albumin > 30 g/L
- Aspartate aminotransferase (AST) < 3 times the ULN
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For male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of 177Lu-PSMA-617.
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Patient must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Presence of a very high-risk feature: cT3b to T4 OR primary pattern 5 OR 2 to 3 high-risk features OR >4 cores with Grade Group 4 or 5.
- Any prior pharmacotherapy (with the exception of up to 45 days of ADT prior to randomization), radiation therapy, or surgery as treatment for prostate cancer. Any prior radiopharmaceutical therapy.
- Any prior radiation to the pelvis.
- Presence of N1 or M1 disease by conventional imaging (CT, MRI, and/or bone scan) or M1 disease by PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL). Lymph nodes with short axis > 8 mm by CT will be considered N1 by conventional imaging.
- Castration-resistant prostate cancer (CRPC).
- Patient receiving any other investigational agents.
- Patient is participating in a concurrent treatment protocol involving radiotherapy, surgery, or systemic anti-cancer agents.
- Inadequate bone marrow reserve and organ function as detailed in 5.1.10.
- Unable to lie flat during or tolerate PET/MRI, PET/CT or EBRT.
- Concurrent serious medical condition that, in the opinion of the Investigator, would impair study participation.
- Contraindication to receiving pelvic radiation, including history of or active inflammatory bowel disorders.
- Refusal to sign informed consent.
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 |
|---|---|
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実験的：Arm A (EBRT + 6 mo ADT + 177Lu-PSMA-617)
Participants will receive EBRT + 6 mo ADT + 177Lu-PSMA-617 |
In Arm A, 177Lu-PSMA-617 will be given as intravenous infusion every 6 weeks, up to 4 cycles. Cycle 1 Day 1 (C1D1) of 177Lu-PSMA-617 will start at least 2 weeks after ADT, and EBRT will start at least 2 weeks after C1D1. |
|
アクティブコンパレータ：Arm B (EBRT + 24 mo ADT)
Participants will receive EBRT + 24 mo ADT |
In Arm B, EBRT will start 3-7 weeks after Day 1 of ADT. |
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 |
|---|---|---|
|
Rate of testosterone recovery (TR)
時間枠：Post randomization up to 3 years.
|
The rate of testosterone recovery (TR) will be determined by the percentage of patients who recover normal T levels within 3 years after randomization. |
Post randomization up to 3 years.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Biochemical disease-free survival (BC-DFS)
時間枠：From randomization up to 3 years.
|
Measured from randomization to the time of a measured PSA value at least 2 ng/mL above nadir, and at least 25% above nadir, or death, whichever occurs first. |
From randomization up to 3 years.
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Time-to-Next-Intervention (TTNI)
時間枠：From randomization up to 3 years.
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TTNI is defined as the period of time from randomization to the initiation of any additional cancer-directed therapy. In the absence of a defining event, TTNI will be censored at the date of last visit documenting absence of interventions. |
From randomization up to 3 years.
|
|
ADT-free survival (ADT-FS)
時間枠：From randomization up to 3 years.
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ADT-free survival defined as the time from randomization to the time of initiation of palliative ADT or death, whichever occurs first. |
From randomization up to 3 years.
|
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Metastasis-free survival (MFS)
時間枠：From randomization up to 3 years.
|
MFS is defined as the time from randomization to the time of detection of at least one new metastatic lesions on conventional imaging. Patients who do not develop at least one new metastasis will be censored at the time of the last disease assessment. |
From randomization up to 3 years.
|
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Overall Survival (OS)
時間枠：From randomization to the date of death, up to 3 years.
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For subjects who do not die, time to death will be censored at the time of last contact. |
From randomization to the date of death, up to 3 years.
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Toxicity as assessed by adverse events
時間枠：In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).
|
Toxicity of combination therapy with EBRT + 6 mo ADT + 177Lu-PSMA-617 by collecting CTCAE v5.0 adverse events. |
In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).
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Quality of Life as assessed by Expanded Prostate Index Composite (EPIC)
時間枠：Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
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Score range, 0-100. Higher score better quality of life. |
Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
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Quality of Life as assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30
時間枠：Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
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Score range from 0 to 100. A higher score indicates better quality of life. |
Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
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Quality of Life as assessed by Xerostomia Quality of Life Scale (XeQoLS)
時間枠：Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
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Score range 0 to 60, with higher scores indicating worse quality of life. |
Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).
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Correlation of Toxicities and Absorbed Dose
時間枠：In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).
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To correlate rate of CTCAE v5.0 grade 3 toxicities with mean absorbed dose to normal organs at risk. Specifically, pelvic organ toxicities will be correlated with mean EBRT dose, mean Lu-PSMA absorbed dose and mean cumulative absorbed dose for the bladder, rectum, and bowel. |
In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).
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協力者と研究者
捜査官
- 主任研究者：Ana Kiess、Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
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 (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
- J25104
- IRB00494892 (その他の識別子：Johns Hopkins Medicine IRB)
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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