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

Solid Tumor Clinical Trial

Official title:

Safety and Tolerability of Low Dose Radiotherapy Plus Concurrent Partial Stereotactic Ablative Radiotherapy (Eclipse-RT) and Tislelizumab in Patients With Bulky Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06349837
• Other study ID #: ECLIPSE-02
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 15, 2024
• Est. completion date: March 31, 2026

Study information

• Verified date: March 2024
• Source: Sichuan University
• Contact: Ren Luo, MD
• Phone: 18349337131
• Email: luorenbu[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is 3+3 escalation phase I study which will be conducted in West China Hospital. 3 patients per cohort (a total of 9 patients) will be enrolled to observe the dose-limiting toxicity (DLT) and recommended dose for expansion (RDE) for lung LDRT and partial SBRT. All eligible patients will receive LDRT + partial SBRT and Tislelizumab at different dose levels (decried as below). Tislelizumab will be given at 200mg as recommended in the instruction manual every 3 weeks until disease progression, unacceptable toxicities, the patient withdraws informed consent, or Tislelizumab reaches a maximum of up to 24 months. Patients in the dose escalation will receive LDRT + partial SBRT at 3 cohorts with increasing dose levels: 6 Gy (2 Gy/f) + 24 Gy (8 Gy/f); 6 Gy (2 Gy/f) + 30 Gy (10 Gy/f); 6 Gy (2 Gy/f) + 45 Gy (15 Gy/f).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial.

2. Be =18 years of age on day of signing informed consent.

3. Patients with histologically or cytologically confirmed stage IV NSCLC.

4. Be willing to undergo repeat biopsy of tumor lesions according to the study protocol.

5. Patients who have failed the standard therapy, or who are unsuitable for standard treatment, or refuse chemotherapy.

6. 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.

7. The target lesions (irradiated lesions) are > 5cm in in diameter

8. ECOG 0-2.

9. Life expectancy of > 3 months.

10. Subjects should agree to use an adequate method of contraception.

Exclusion Criteria:

1. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or spinal cord compression, etc.

2. With oncologic emergencies that require immediate treatment

3. EGFR/ALK/ROS-1 mutation or mutation status unknown.

4. Has evidence of interstitial lung disease or active and/or non-infectious pneumonitis (drug-induced pneumonia, radiation-induced pneumonia, etc.) requiring steroid therapy.

5. History of pulmonary fibrosis, pulmonary hypertension, severe irreversible airway obstruction disease

6. Patients with peripheral neuropathy.

7. Significant heart disease or impairment of cardiac function

8. Fluid accumulating in the third space, such as pericardial effusion, pleural effusion and peritoneal effusion that remains uncontrolled by aspiration or other treatment

9. Known allergy to drugs or excipients, known severe allergic reaction to any of the PD-1 monoclonal antibodies

10. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.

Related Conditions & MeSH terms

• Solid Tumor

Intervention

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

Radiation:
• Low Dose Radiotherapy
LDRT (d1-d3): 6Gy/3f with conventional external beam radiation.
• Stereotactic Ablative Radiotherapy
Partial SBRT at dose escalation levels: 24Gy/3f, 30Gy/3f, 45Gy/3f.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan University

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities		24 months
Secondary	Objective Response Rate (ORR)	The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.	up to 24 months after the enrollment
Secondary	Progression Free Survival (PFS)	Investigator assessed PFS according to RECIST v1.1. Progression free survival is defined as time of enrollment to first evidence of progressive disease.	up to 24 months after the enrollment
Secondary	Overall Survival (OS)	OS is defined as the difference (in months) between the date of study enrollment to the date death due to any cause	up to 24 months after the enrollment