Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery
2021年4月20日 更新者:University of Michigan Rogel Cancer Center
This is a study to test the efficacy of using standard immune therapy for melanoma prior to stereotactic radiosurgery (ipilimumab induction), as compared to stereotactic radiosurgery followed by immune therapy.
The study's hypothesis is that ipilimumab induction is as good as or better than controlling brain metastases as compared to stereotactic radiosurgery followed by immune therapy.
調査の概要
詳細な説明
This is a randomized Phase II selection study investigating the use of ipilimumab induction prior to stereotactic radiosurgery (SRS), versus no induction, for melanoma brain metastases.
Participants will be randomized to Arm A "Induction" (two doses of ipilimumab prior to SRS, two doses of ipilimumab after SRS) versus Arm B "No induction" (SRS first, followed by 4 doses of ipilimumab).
Participants will undergo multiple dynamic contrast-enhanced MRIs of the brain and submit blood samples for immune testing.
研究の種類
介入
入学 (実際)
4
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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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- University of Michigan Hospital
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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
全て
説明
Inclusion Criteria:
- Patients with a histologically-confirmed diagnosis of melanoma who have imaging findings suggestive of 1 to 4 brain metastases
- At least one lesion in the brain that is measurable, which is defined as ≥5 x 5mm (Prior craniotomy and surgical resection is allowed, as long as there is at least one remaining measurable lesion in the brain)
- Patients must be candidates for stereotactic radiosurgery (SRS) and planning to undergo SRS
- Patients must be candidates for ipilimumab as determined by the treating physician
- Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged by the treating physicians
- At least 3 weeks has elapsed from any prior therapy, and the patient has recovered from side effects to ≤ grade 1 toxicities per Common Terminology Criteria (CTC) for Adverse Events
- Age > or = 18 years old
- Performance status of ECOG of 0 or 1 (ECOG is the Eastern Oncology Cooperative Group Scoring system used to quantify cancer patients' general well-being and activities of daily life; scores range from 0 to 5 where 0 is perfect health and 5 is death)
- Adequate organ and marrow function: alanine aminotransferase (ALT ) < 2.5x's upper limit of normal (ULN) of the institutional normal reference range, aspartate aminotransferase (AST) < 2.5x's ULN of the institutional normal reference range, Bilirubin < 1.5x's ULN of the institutional normal reference range, Creatinine < 2.0 milligrams per deciliter, Platelets > 50,000 per microliter
- Women of child-bearing potential must agree to use adequate contraception, defined as complete abstinence from intercourse with men or two methods
- Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
- Previous radiotherapy to the lesion(s) of interest, including prior treatment with whole brain radiation therapy (WBRT). Prior treatment with SRS is allowed if the index lesion(s) is in a different, non-contiguous location than the previously treated lesion.
- Patients who have previously received ipilimumab, PD-1 inhibitors or PD-L1 inhibitors are excluded due to the potential of effects on primary outcome
- Patients who require WBRT or surgery at the time of enrollment
- Neurologic symptoms or imaging findings that necessitate the use of steroids on the day of enrollment or in the prior 7 days
- Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid evidence of leptomeningeal metastases, unless all measurable disease is localized and SRS is considered the treatment of choice
- Concurrent treatment with any other anti-neoplastic drug or concurrent participation in another therapeutic clinical trial
- Patients unable to undergo or tolerate MRI scans (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, history of allergic reaction/hypersensitivity to gadolinium)
- Women who are pregnant or are nursing
- Patients with absolute lymphocyte count of <500 cells/microliter, who are known to be HIV positive, who have clinically significant active autoimmune disease, or are receiving immunosuppression following solid organ or stem cell transplant
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: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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アクティブコンパレータ:B: No induction
Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses.
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Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses.
Stereotactic radiosurgery is a type of focused radiation therapy.
It requires the placement of a metal frame on the head for several hours.
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実験的:A: Induction
Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses.
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Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses.
Stereotactic radiosurgery is a type of focused radiation therapy.
It requires the placement of a metal frame on the head for several hours.
|
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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Local Control Rate
時間枠:6 months
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The number of patients in each arm who are free from progression in the index (radiated) lesions in the brain at 6 months. Immune related response criteria was used to assess response to treatment. Immune-related Progressive Disease (irPD) in this trial is defined as an increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented. |
6 months
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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 |
---|---|---|
Overall Survival Rate
時間枠:Up to 5 years
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Number of participants alive at 5 years after enrollment.
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Up to 5 years
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Regional (Intracranial) Control Rate
時間枠:6 months
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The proportion of patients in each arm who are free from progression in the index (radiated) lesions and free from new brain metastases at 6 months.
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6 months
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Intracranial Response Rate
時間枠:Up to 12 months
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Response of treated (irradiated) brain metastases to combination therapy with ipilimumab and stereotactic radiosurgery using immune-related response criteria.
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Up to 12 months
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Time to Progression
時間枠:From date of enrollment to up to 2 years
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Time to progression in the brain due to treated metastases or new brain metastases.
Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) was used to assess response.
Progression was defined as an increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden), with confirmation by a repeat, consecutive assessment no less than 4 wk from the date first documented.
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From date of enrollment to up to 2 years
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
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Imaging Correlates on Dynamic-contrast Enhanced MRI of the Brain
時間枠:6 months
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Exploratory endpoints: Interval changes in dynamic MRI parameters such as perfusion, blood volume, vascular permeability (Ktrans), and diffusion tensor imaging; the change in 3D tumor volume.
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6 months
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Immune Correlates
時間枠:6 months
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Exploratory endpoints: Interval changes in immune markers in the blood
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6 months
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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。
捜査官
- 主任研究者:Christopher Lao, M.D.、University of Michigan Rogel Cancer Center
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
2014年4月1日
一次修了 (実際)
2016年8月1日
研究の完了 (実際)
2020年7月1日
試験登録日
最初に提出
2014年3月24日
QC基準を満たした最初の提出物
2014年3月24日
最初の投稿 (見積もり)
2014年3月27日
学習記録の更新
投稿された最後の更新 (実際)
2021年5月12日
QC基準を満たした最後の更新が送信されました
2021年4月20日
最終確認日
2021年4月1日
詳しくは
本研究に関する用語
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Ipilimumabの臨床試験
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Celldex Therapeutics終了しました
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Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)募集