Proton and Proton-Photon Hybrid Partial Stereotactic Ablative Boost Radiotherapy (P-SABR) for Unresectable Large Tumors (LARGE-Proton)
2026年9月9日 更新者：Xian-shu Gao、Peking University First Hospital
A Prospective, Multicenter, Observational Cohort Study of Proton and Proton-Photon Hybrid Partial Stereotactic Ablative Boost Radiotherapy (P-SABR) for Unresectable Large Tumors
This prospective, multicenter, observational cohort study will enroll 60 adults with unresectable larege tumors (longest diameter > 5 cm) who receive one of two treatment modes: (A) proton P-SABR, in which both the proton partial-SABR boost (course 1) and the subsequent proton CFRT (course 2) are delivered at the proton center; or (B) proton-photon hybrid P-SABR, in which course 1 is delivered with protons at the proton center and course 2 CFRT is delivered with photons.
The primary objective is to describe, in each cohort, the incidence of treatment-related grade ≥ 3 acute and late adverse events (CTCAE v5.0).
Secondary objectives are dosimetric and the 1-year local control rate (RECIST 1.1, in-field).
Participants are followed for up to 5 years.
調査の概要
詳細な説明
BACKGROUND Large tumors (longest diameter > 5 cm) are often unresectable and respond poorly to conventionally fractionated radiotherapy (CFRT) because of their size and hypoxic core, while normal-tissue tolerance prevents delivering stereotactic ablative radiotherapy (SABR) to the whole tumor. Partial stereotactic ablative boost radiotherapy (P-SABR) delivers a SABR boost only to the central part of a large tumor, followed by CFRT to the whole target. Proton beams, with their Bragg-peak dose fall-off, may sharpen this "onion-skin" dose distribution and further increase the biologically effective dose (BED) within the tumor core.
DESIGN This prospective, multicenter, observational cohort study will enroll 60 adults with unresectable bulky tumors (longest diameter > 5 cm) who, as part of routine care, receive one of two treatment modes: (A) proton P-SABR, in which both the proton partial-SABR boost (course 1) and the subsequent proton CFRT (course 2) are delivered at the proton center; or (B) proton-photon hybrid P-SABR, in which course 1 is delivered with protons at the proton center and course 2 CFRT is delivered with photons (IMRT/VMAT) either at the same center or at Peking University First Hospital or one of six photon sub-centers, after central review of the composite plan. Cohort membership follows the patient's own choice and care pathway; the study does not assign treatment or intervene in clinical decisions, and no formal between-cohort hypothesis testing is planned.
OUTCOMES The primary objective is to describe, in each cohort, the incidence of treatment-related grade ≥ 3 acute and late adverse events (CTCAE v5.0). Secondary objectives are dosimetric (percentage of the GTV receiving BED10 ≥ 100 Gy, PTV V95% and V100%, organ-at-risk doses) and the 1-year local control rate (RECIST 1.1, in-field). Participants are followed for up to 5 years.
研究の種類
観察的
入学 (推定)
60
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。
研究連絡先
- 名前：Xianshu Gao, MD, PhD
- 電話番号：010-83575239
- メール：doctorgaoxs@126.com
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
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
サンプリング方法
非確率サンプル
調査対象母集団
Adults with histologically or cytologically confirmed, unresectable bulky solid tumors (at least one lesion with longest diameter > 5 cm) who present to the radiation oncology departments of the participating centers, and who elect to receive proton P-SABR (Cohort A) or proton-photon hybrid P-SABR (Cohort B).
Eligible patients are enrolled consecutively after written informed consent.
説明
Inclusion Criteria:
- Histologically or cytologically confirmed malignancy
- At least one tumor with a longest diameter > 5 cm
- Not amenable to curative surgical resection, or patient declines surgery, or surgery contraindicated because of medical comorbidities
- Age ≥ 18 years
- ECOG performance status 0-2
- Life expectancy > 3 months
- Written informed consent
Exclusion Criteria:
- Prior radiotherapy to the same site
- Severe cardiopulmonary insufficiency precluding radiotherapy
- Concurrent other active malignancy
- Uncontrolled acute infection or bowel obstruction
- Pregnancy or breastfeeding
- Intracranial lesion
- Tumor directly invading the full thickness of the esophageal, gastric or intestinal wall with active ulceration, fistula or uncontrolled risk of perforation (tumors that only abut or displace a hollow organ without full-thickness invasion are not excluded)
- Uncontrolled active tumor bleeding, or impending pathological fracture requiring orthopedic intervention
- Any other condition that, in the investigator's judgment, makes the patient unsuitable for the 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
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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Cohort A: Proton P-SABR
Participants who receive the entire P-SABR course with protons at Hebei Yizhou Cancer Hospital: course 1, proton partial stereotactic ablative boost (intensity-modulated proton therapy, IMPT); course 2, proton conventionally fractionated radiotherapy (CFRT).
Planned enrollment: 30.
|
Course 1 (proton partial-SABR boost, IMPT): CTV 1.8-3 Gy per fraction with a simultaneous boost to the boost volume within the GTV (GTVb) of 8 Gy × 3 fractions; in larger tumors the inner GTVb (GTVb shrunk by 1 cm) is further boosted to 12 Gy × 3 fractions; critical organs at risk < 3 Gy per fraction; robust optimization on the CTV.
Course 2 (proton CFRT): CTV 1.8-3 Gy per fraction with robust optimization, to a cumulative PTV dose of 60-70 Gy on the summed plan, with GTVb BED10 ≥ 100 Gy.
Proton dose is expressed with a constant RBE of 1.1.
Both courses are delivered at Hebei Yizhou Cancer Hospital.
他の名前：
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Cohort B: Proton-Photon Hybrid P-SABR
Participants who receive course 1 (proton partial stereotactic ablative boost, IMPT) at Hebei Yizhou Cancer Hospital, followed by course 2 photon conventionally fractionated radiotherapy (IMRT/VMAT with daily CBCT) delivered either at the same center (pathway A, same-center; planned n = 10) or at Peking University First Hospital or one of six photon sub-centers (pathway B, cross-center; planned n = 20) after central review of the composite plan.
Planned enrollment: 30.
|
Course 1 identical to Cohort A: proton partial-SABR boost (IMPT) with GTVb 8 Gy × 3 fractions and inner GTVb 12 Gy × 3 fractions, delivered at Hebei Yizhou Cancer Hospital.
Course 2 (photon CFRT): IMRT/VMAT with daily CBCT recommended, PTV 1.8-3 Gy per fraction to a cumulative PTV dose of 60-70 Gy on the summed plan, with GTVb BED10 ≥ 100 Gy, delivered at Hebei Yizhou Cancer Hospital (same-center) or at Peking University First Hospital or a photon sub-center (cross-center).
For cross-center participants, DICOM-RT structure, plan and dose files of both courses are reviewed by the central radiotherapy QA committee, which performs deformable registration and dose summation (MIM; proton RBE = 1.1) before course 2 starts.
Target interval between courses ≤ 3 working days (maximum 7 working days).
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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Incidence of treatment-related adverse events of grade ≥ 3 (CTCAE v5.0)
時間枠：From the first fraction of radiotherapy to the end of the study
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Up to 5 years after completion of radiotherapy (acute events: from the first fraction of radiotherapy through 90 days after completion; late events: from day 91 after completion through 5 years)
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From the first fraction of radiotherapy to the end of the study
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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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Percentage of the gross tumor volume (GTV) receiving a biologically effective dose (BED10) ≥ 100 Gy
時間枠：Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)
|
Volume fraction (%) of the GTV receiving BED10 ≥ 100 Gy on the composite (summed) plan, extracted from the treatment planning system (proton dose converted with RBE = 1.1; dose summation in MIM ).
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Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)
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Planning target volume (PTV) coverage: V95% and V100%
時間枠：Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)
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Percentage of the PTV receiving ≥ 95% (V95%) and ≥ 100% (V100%) of the prescribed cumulative dose on the composite plan, reported per cohort as mean ± SD.
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Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)
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Doses to organs at risk (OARs)
時間枠：Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)
|
Dose metrics of organs at risk (e.g., spinal cord maximum dose, esophagus, lung, bowel, brachial plexus) on the composite plan, and the proportion of participants meeting each OAR dose constraint, reported per OAR and per cohort with 95% CI.
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Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)
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1-year local control (LC) rate
時間枠：12 months after the first fraction of radiotherapy
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Local control is defined as the absence of progressive disease (RECIST 1.1) in in-field lesions; the in-field region is defined by the GTV/CTV/PTV projections exported from the treatment planning system (DICOM-RT) and confirmed by blinded central imaging review.
Time to local progression is measured from the first fraction of radiotherapy.
The 1-year LC rate and its Greenwood 95% CI are estimated per cohort with the Kaplan-Meier method; no between-cohort test is performed.
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12 months after the first fraction of radiotherapy
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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。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Bai Y, Gao XS, Qin SB, Chen JY, Su MM, Liu Q, Qin XB, Ma MW, Zhao B, Gu XB, Xie M, Cui M, Qi X, Li XY. Partial stereotactic ablative boost radiotherapy in bulky non-small cell lung cancer: a retrospective study. Onco Targets Ther. 2018 May 8;11:2571-2579. doi: 10.2147/OTT.S159538. eCollection 2018.
- Bai Y, Gao X, Qin S, Li S, Ma M, Cao X, Lyu F, Chen J, Qi X, Liu S, Gao Y, Li H, Li X, Li X, Ren X, Huang L. Partial Stereotactic Ablative Radiotherapy Boost Before Conventional Radiotherapy (P-SABR) for Large (> 5 cm) Unresectable Stage III Nonsmall Cell Lung Cancer. Thorac Cancer. 2025 Jan;16(2):e15514. doi: 10.1111/1759-7714.15514. Epub 2024 Dec 14.
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 (推定)
2026年10月1日
一次修了 (推定)
2029年12月1日
研究の完了 (推定)
2029年12月1日
試験登録日
最初に提出
2026年9月3日
QC基準を満たした最初の提出物
2026年9月9日
最初の投稿 (実際)
2026年9月14日
学習記録の更新
投稿された最後の更新 (実際)
2026年9月14日
QC基準を満たした最後の更新が送信されました
2026年9月9日
最終確認日
2026年9月1日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- LARGE-Proton-001
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?
いいえ
IPD プランの説明
Individual participant data will not be made publicly available because of Chinese regulations on health data and human genetic resources.
De-identified data may be shared with qualified researchers on reasonable request to the principal investigator, subject to ethics committee approval.
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米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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