Safety and Tolerability of LDRT Plus Concurrent Partial SBRT and Tislelizumab in Patients With Bulky Tumors

NCT06349837 | Recruiting Phase 1

• 1 other identifier: ECLIPSE-02
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 3+3 dose escalation phase I study which aims to evaluate the safety and tolerability of low dose radiotherapy (LDRT) plus concurrent partial Stereotactic Ablative Radiotherapy (SBRT) and Tislelizumab in Patients with bulky tumors who have failed standard therapy. At least 9 participants will be enrolled in this study.

Conditions

Solid Tumor

Keywords

Low Dose Radiotherapy; Stereotactic Ablative Radiotherapy; Tislelizumab

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities

  24 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  up to 24 months after the enrollment

• Progression Free Survival (PFS)

  up to 24 months after the enrollment

• Overall Survival (OS)

  up to 24 months after the enrollment

Study Arms (1)

LDRT+SBRT + Tislelizumab

EXPERIMENTAL

This is a dose escalation study, low Dose Radiotherapy (LDRT) dose was 6Gy/3f, Stereotactic Ablative Radiotherapy (SBRT) dose was 24Gy/3f , 30Gy/3f and 45 Gy/3f, the dose of Tislelizumab was recommended in the instruction manual.

Drug: Tislelizumab; Radiation: Low Dose Radiotherapy; Radiation: Stereotactic Ablative Radiotherapy

Interventions

Tislelizumab DRUG

Patients will receive treatment with Tislelizumab (200 mg, iv, d1), every 3 weeks for a maximum of 48 months.

Also known as: PD-1 inhibitor

LDRT+SBRT + Tislelizumab

Low Dose Radiotherapy RADIATION

LDRT (d1-d3): 6Gy/3f with conventional external beam radiation.

Also known as: LDRT

LDRT+SBRT + Tislelizumab

Stereotactic Ablative Radiotherapy RADIATION

Partial SBRT at dose escalation levels: 24Gy/3f, 30Gy/3f, 45Gy/3f.

Also known as: SBRT

LDRT+SBRT + Tislelizumab

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥18 years of age on day of signing informed consent.
• Patients with histologically or cytologically confirmed stage IV solid tumours.
• Be willing to undergo repeat biopsy of tumor lesions according to the study protocol.
• Patients who have failed the standard therapy, or who are unsuitable for standard treatment, or refuse chemotherapy.
• At least one measurable lesion according to RECIST 1.1. A lesion that has previously received radiotherapy can be considered a target lesion only if this lesion is clearly progressed after radiotherapy.
• The target lesions (irradiated lesions) are \> 5cm in in diameter
• ECOG 0-2.
• Life expectancy of \> 3 months.
• Subjects should agree to use an adequate method of contraception.

You may not qualify if:

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or spinal cord compression, etc.
• With oncologic emergencies that require immediate treatment
• EGFR/ALK/ROS-1 mutation or mutation status unknown.
• Has evidence of interstitial lung disease or active and/or non-infectious pneumonitis (drug-induced pneumonia, radiation-induced pneumonia, etc.) requiring steroid therapy.
• History of pulmonary fibrosis, pulmonary hypertension, severe irreversible airway obstruction disease
• Patients with peripheral neuropathy.
• Significant heart disease or impairment of cardiac function
• Fluid accumulating in the third space, such as pericardial effusion, pleural effusion and peritoneal effusion that remains uncontrolled by aspiration or other treatment
• Known allergy to drugs or excipients, known severe allergic reaction to any of the PD-1 monoclonal antibodies
• Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (8)

• Yin L, Xue J, Li R, Zhou L, Deng L, Chen L, Zhang Y, Li Y, Zhang X, Xiu W, Tong R, Gong Y, Huang M, Xu Y, Zhu J, Yu M, Li M, Lan J, Wang J, Mo X, Wei Y, Niedermann G, Lu Y. Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):212-224. doi: 10.1016/j.ijrobp.2020.05.002. Epub 2020 May 15.

  PMID: 32417411 BACKGROUND

• Lan J, Li R, Yin LM, Deng L, Gui J, Chen BQ, Zhou L, Meng MB, Huang QR, Mo XM, Wei YQ, Lu B, Dicker A, Xue JX, Lu Y. Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy. Int J Radiat Oncol Biol Phys. 2018 May 1;101(1):74-87. doi: 10.1016/j.ijrobp.2018.01.071. Epub 2018 Mar 12.

  PMID: 29619980 BACKGROUND

• Zhou X, Zhou L, Yao Z, Huang M, Gong Y, Zou B, Zhu J, Liu Y, Peng F, Zhang Y, Yu M, Li Y, Na F, Wu Y, Kang K, Xiu W, Zhang X, Zhou L, Xu Y, Wang J, Wang Y, Yang X, Wu Y, Li R, Zhang Y, Yang Z, Zhou Z, Bai J, Yi X, Tong R, Yin L, Chen C, Niedermann G, Lu Y, Xue J. Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naive Stage IV PD-L1+ Non-Small Cell Lung Cancer Patients. Clin Cancer Res. 2023 Oct 13;29(20):4098-4108. doi: 10.1158/1078-0432.CCR-23-0315.

  PMID: 37581611 BACKGROUND

• Zhou L, Liu Y, Wu Y, Yang X, Spring Kong FM, Lu Y, Xue J. Low-dose radiation therapy mobilizes antitumor immunity: New findings and future perspectives. Int J Cancer. 2024 Apr 1;154(7):1143-1157. doi: 10.1002/ijc.34801. Epub 2023 Dec 7.

  PMID: 38059788 BACKGROUND

• Barsoumian HB, Ramapriyan R, Younes AI, Caetano MS, Menon H, Comeaux NI, Cushman TR, Schoenhals JE, Cadena AP, Reilly TP, Chen D, Masrorpour F, Li A, Hong DS, Diab A, Nguyen QN, Glitza I, Ferrarotto R, Chun SG, Cortez MA, Welsh J. Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma. J Immunother Cancer. 2020 Oct;8(2):e000537. doi: 10.1136/jitc-2020-000537.

  PMID: 33106386 BACKGROUND

• Barsoumian HB, Sezen D, Menon H, Younes AI, Hu Y, He K, Puebla-Osorio N, Wasley M, Hsu E, Patel RR, Yang L, Cortez MA, Welsh JW. High Plus Low Dose Radiation Strategy in Combination with TIGIT and PD1 Blockade to Promote Systemic Antitumor Responses. Cancers (Basel). 2022 Jan 3;14(1):221. doi: 10.3390/cancers14010221.

  PMID: 35008385 BACKGROUND

• Menon H, Chen D, Ramapriyan R, Verma V, Barsoumian HB, Cushman TR, Younes AI, Cortez MA, Erasmus JJ, de Groot P, Carter BW, Hong DS, Glitza IC, Ferrarotto R, Altan M, Diab A, Chun SG, Heymach JV, Tang C, Nguyen QN, Welsh JW. Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy. J Immunother Cancer. 2019 Sep 4;7(1):237. doi: 10.1186/s40425-019-0718-6.

  PMID: 31484556 BACKGROUND

• Welsh JW, Tang C, de Groot P, Naing A, Hess KR, Heymach JV, Papadimitrakopoulou VA, Cushman TR, Subbiah V, Chang JY, Simon GR, Ramapriyan R, Barsoumian HB, Menon H, Cortez MA, Massarelli E, Nguyen Q, Sharma P, Allison JP, Diab A, Verma V, Raju U, Shaaban SG, Dadu R, Cabanillas ME, Wang K, Anderson C, Gomez DR, Hahn S, Komaki R, Hong DS. Phase II Trial of Ipilimumab with Stereotactic Radiation Therapy for Metastatic Disease: Outcomes, Toxicities, and Low-Dose Radiation-Related Abscopal Responses. Cancer Immunol Res. 2019 Dec;7(12):1903-1909. doi: 10.1158/2326-6066.CIR-18-0793. Epub 2019 Oct 28.

  PMID: 31658994 BACKGROUND

MeSH Terms

Interventions

tislelizumab; Immune Checkpoint Inhibitors; Radiotherapy

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Study Officials

• You Lu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ren Luo, MD

CONTACT

18349337131; luorenbu@163.com

Li Li, BA

CONTACT

02885424619; tracy.li_2010@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Department of Thoracic Cancer

Study Record Dates

• First Submitted: March 31, 2024
• First Posted: April 5, 2024
• Study Start: April 18, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)