Proton and Proton-Photon Hybrid Partial Stereotactic Ablative Boost Radiotherapy (P-SABR) for Unresectable Large Tumors

NCT07818798 | Not Yet Recruiting DMC

• 1 other identifier: LARGE-Proton-001
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Unresectable Malignant Neoplasm; Bulky Tumor; Solid Tumor

Keywords

partial stereotactic ablative boost radiotherapy; P-SABR; proton therapy; proton-photon hybrid radiotherapy; bulky tumor; large tumor; stereotactic ablative radiotherapy; spatially fractionated radiotherapy; biologically effective dose; conventionally fractionated radiotherapy

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related adverse events of grade ≥ 3 (CTCAE v5.0)

  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)

  From the first fraction of radiotherapy to the end of the study

Secondary Outcomes (4)

• Percentage of the gross tumor volume (GTV) receiving a biologically effective dose (BED10) ≥ 100 Gy

  Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)

• Planning target volume (PTV) coverage: V95% and V100%

  Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)

• Doses to organs at risk (OARs)

  Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized)

• 1-year local control (LC) rate

  12 months after the first fraction of radiotherapy

Study Arms (2)

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.

Radiation: Proton P-SABR

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.

Radiation: Proton-Photon Hybrid P-SABR

Interventions

Proton P-SABR RADIATION

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.

Also known as: Proton partial stereotactic ablative boost radiotherapy, Proton partial-SABR boost followed by proton conventionally fractionated radiotherapy

Cohort A: Proton P-SABR

Proton-Photon Hybrid P-SABR RADIATION

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).

Also known as: Proton-photon hybrid partial stereotactic ablative boost radiotherapy, Proton partial-SABR boost followed by photon conventionally fractionated radiotherapy

Cohort B: Proton-Photon Hybrid P-SABR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University First Hospital: lead

Related Publications (2)

• 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.

  PMID: 29780250 RESULT

• 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.

  PMID: 39673459 RESULT

Central Study Contacts

Xianshu Gao, MD, PhD

CONTACT

010-83575239; doctorgaoxs@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Department of Radiation Oncology

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 14, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share