Efficacy and Safety of High-Dose Rate Brachytherapy with Immunotherapy and Chemotherapy As Second-Line Treatment for Advanced Non-Small Cell Lung Cancer

NCT06518018 | Active Not Recruiting DMC

• 1 other identifier: lunshen（yan）2023.no 10
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, retrospective, propensity score-matched study exploring the efficacy and safety of high-dose rate (HDR) brachytherapy combined with immune checkpoint inhibitors (ICIs) and chemotherapy as a second-line treatment for advanced non-small cell lung cancer (NSCLC). The study will compare two groups: Study group: HDR brachytherapy (30Gy single fraction) + ICIs (pembrolizumab) + chemotherapy (docetaxel) Control group: ICIs (pembrolizumab) + chemotherapy (docetaxel) alone Primary objective: To assess the objective response rate (ORR) Secondary objectives: To evaluate progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. The study aims to address the unmet clinical need for effective treatments in advanced NSCLC patients who have progressed after immunotherapy. It will investigate whether the addition of HDR brachytherapy to immunotherapy and chemotherapy can improve treatment outcomes. This research is significant as it explores a novel treatment combination, potentially offering new options for second-line treatment of advanced NSCLC. It also aims to contribute to the understanding of how radiotherapy doses affect immunotherapy responses and may help identify biomarkers for treatment response prediction.

Conditions

Advanced Stage NSCLC; Second-line Treatment; Patients Without Targetable Driver Mutations

Keywords

Second-Line Treatment; High-Dose Rate (HDR) Brachytherapy; Non-Small Cell Lung Cancer (NSCLC); Immune Checkpoint Inhibitors (ICIs); Propensity Score-Matched; Advanced Stage

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of patients achieving either a complete response (CR) or partial response (PR) according to RECIST v1.1 criteria

  Every 8 weeks from baseline up to 24 months or until disease progression, unacceptable toxicity, or withdrawal from the study, whichever occurs first

Secondary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-Free Survival was assessed from the date of treatment initiation until the date of first documented disease progression or death from any cause, whichever occurred first, assessed up to 24 months.

Other Outcomes (1)

• Overall Survival (OS)

  Overall Survival was measured from the date of treatment initiation until death from any cause or patients who were still alive at the last follow-up were censored at that time point, assessed up to 36 months.

Study Arms (2)

Study Group

HDR Brachytherapy + Immunotherapy + Chemotherapy Group

Radiation: HDR brachytherapy (30Gy single fraction)

Control Group

Immunotherapy + Chemotherapy Group

Drug: Immunotherapy

Interventions

HDR brachytherapy (30Gy single fraction) RADIATION

Study Group receives a novel triple combination therapy for advanced NSCLC in the second-line setting. The treatment begins with a single fraction of high-dose rate (HDR) brachytherapy, delivering 30 Gy locally to the tumor site. This is followed within 1-3 days by systemic therapy, combining immunotherapy and chemotherapy , both administered intravenously.

Also known as: ICIs, chemotherapy

Study Group

Immunotherapy DRUG

Control Group receives the current standard of care for second-line treatment of advanced NSCLC. This regimen consists of a combination of immunotherapy and chemotherapy , both administered intravenously

Also known as: chemotherapy

Control Group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. Adult patients with advanced Non-Small Cell Lung Cancer (NSCLC) 2. Requiring second-line treatment after progression on initial therapy 3. Likely stage IIIB-IV disease 4. Measurable disease according to RECIST v1.1 criteria 5. Without targetable driver mutations (e.g., EGFR, ALK, ROS1, BRAF) 6. Candidates for immunotherapy and chemotherapy 7. Adequate organ function to tolerate proposed treatments 8. ECOG performance status likely 0-2 9. May have prior exposure to immunotherapy 10. Treated at a single center in China 11. Divided into two groups

You may qualify if:

• Diagnosis of advanced Non-Small Cell Lung Cancer (NSCLC),Likely stage IIIB-IV, though specific staging is not mentioned
• Patients requiring second-line treatment Implying progression after first-line therapy
• Age: Adults (specific age range not provided, but typically 18 years or older)
• Presence of measurable disease according to RECIST v1.1 criteria
• Adequate organ function (specific parameters not provided, but typically included in such studies)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (not explicitly stated, but common in similar studies)

You may not qualify if:

• Presence of targetable driver mutations (e.g., EGFR, ALK, ROS1, BRAF)
• Prior treatment with HDR brachytherapy for the current disease
• Contraindications to immunotherapy or chemotherapy
• Severe comorbidities that would preclude safe administration of study treatments
• Brain metastases, unless treated and stable (not explicitly stated, but common in similar studies)
• Participation in another clinical trial with an investigational agent

Sponsors & Collaborators

• The First People's Hospital of Neijiang: lead

Study Sites (1)

The Second People's Hospital of Neijiang

Neijiang, Sichuan, 641000, China

Location

Related Publications (16)

• Chen HY, Xu L, Li LF, Liu XX, Gao JX, Bai YR. Inhibiting the CD8+ T cell infiltration in the tumor microenvironment after radiotherapy is an important mechanism of radioresistance. Sci Rep. 2018 Aug 9;8(1):11934. doi: 10.1038/s41598-018-30417-6.

  PMID: 30093664 BACKGROUND

• Tateishi Y, Takeda A, Horita N, Tsurugai Y, Eriguchi T, Kibe Y, Sanuki N, Kaneko T. Stereotactic Body Radiation Therapy With a High Maximum Dose Improves Local Control, Cancer-Specific Death, and Overall Survival in Peripheral Early-Stage Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2021 Sep 1;111(1):143-151. doi: 10.1016/j.ijrobp.2021.04.014. Epub 2021 Apr 21.

  PMID: 33891980 BACKGROUND

• Weichselbaum RR, Liang H, Deng L, Fu YX. Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol. 2017 Jun;14(6):365-379. doi: 10.1038/nrclinonc.2016.211. Epub 2017 Jan 17.

  PMID: 28094262 BACKGROUND

• Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7. doi: 10.1038/nature14292. Epub 2015 Mar 9.

  PMID: 25754329 BACKGROUND

• Zhang Z, Liu X, Chen D, Yu J. Radiotherapy combined with immunotherapy: the dawn of cancer treatment. Signal Transduct Target Ther. 2022 Jul 29;7(1):258. doi: 10.1038/s41392-022-01102-y.

  PMID: 35906199 BACKGROUND

• Wu M, Liu J, Wu S, Liu J, Wu H, Yu J, Meng X. Systemic Immune Activation and Responses of Irradiation to Different Metastatic Sites Combined With Immunotherapy in Advanced Non-Small Cell Lung Cancer. Front Immunol. 2021 Dec 14;12:803247. doi: 10.3389/fimmu.2021.803247. eCollection 2021.

  PMID: 34970277 BACKGROUND

• Chen D, Song X, Wang H, Gao Z, Meng W, Chen S, Ma Y, Wang Y, Li K, Yu J, Yue J. Previous Radiotherapy Increases the Efficacy of IL-2 in Malignant Pleural Effusion: Potential Evidence of a Radio-Memory Effect? Front Immunol. 2018 Dec 11;9:2916. doi: 10.3389/fimmu.2018.02916. eCollection 2018.

  PMID: 30619280 BACKGROUND

• Ko EC, Raben D, Formenti SC. The Integration of Radiotherapy with Immunotherapy for the Treatment of Non-Small Cell Lung Cancer. Clin Cancer Res. 2018 Dec 1;24(23):5792-5806. doi: 10.1158/1078-0432.CCR-17-3620. Epub 2018 Jun 26.

  PMID: 29945993 BACKGROUND

• Shabason JE, Minn AJ. Radiation and Immune Checkpoint Blockade: From Bench to Clinic. Semin Radiat Oncol. 2017 Jul;27(3):289-298. doi: 10.1016/j.semradonc.2017.03.002. Epub 2017 Mar 16.

  PMID: 28577836 BACKGROUND

• Taniguchi Y, Shimokawa T, Takiguchi Y, Misumi T, Nakamura Y, Kawashima Y, Furuya N, Shiraishi Y, Harada T, Tanaka H, Miura S, Uchiyama A, Nakahara Y, Tokito T, Naoki K, Bessho A, Goto Y, Seike M, Okamoto H. A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naive Non-Small Cell Lung Cancer: TORG1630. Clin Cancer Res. 2022 Oct 14;28(20):4402-4409. doi: 10.1158/1078-0432.CCR-22-1687.

  PMID: 35980349 BACKGROUND

• Gandhi SJ, Minn AJ, Vonderheide RH, Wherry EJ, Hahn SM, Maity A. Awakening the immune system with radiation: Optimal dose and fractionation. Cancer Lett. 2015 Nov 28;368(2):185-90. doi: 10.1016/j.canlet.2015.03.024. Epub 2015 Mar 20.

  PMID: 25799953 BACKGROUND

• Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB, Ahn MJ, Eder JP, Balmanoukian AS, Aggarwal C, Horn L, Patnaik A, Gubens M, Ramalingam SS, Felip E, Goldman JW, Scalzo C, Jensen E, Kush DA, Hui R. Five-Year Overall Survival for Patients With Advanced Non-Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol. 2019 Oct 1;37(28):2518-2527. doi: 10.1200/JCO.19.00934. Epub 2019 Jun 2.

  PMID: 31154919 BACKGROUND

• Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2.

  PMID: 35108059 BACKGROUND

• Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score >/= 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. doi: 10.1200/JCO.21.00174. Epub 2021 Apr 19.

  PMID: 33872070 BACKGROUND

• Shi JF, Wang L, Wu N, Li JL, Hui ZG, Liu SM, Yang BY, Gao SG, Ren JS, Huang HY, Zhu J, Liu CC, Fan JH, Zhao SJ, Xing PY, Zhang Y, Li N, Lei WD, Wang DB, Huang YC, Liao XZ, Xing XJ, Du LB, Yang L, Liu YQ, Zhang YZ, Zhang K, Qiao YL, He J, Dai M; LuCCRES Group. Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: Overall design and results from a multicenter retrospective epidemiologic survey. Lung Cancer. 2019 Feb;128:91-100. doi: 10.1016/j.lungcan.2018.11.031. Epub 2018 Nov 24.

  PMID: 30642458 BACKGROUND

• Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022 Feb 9;135(5):584-590. doi: 10.1097/CM9.0000000000002108.

  PMID: 35143424 BACKGROUND

MeSH Terms

Conditions

Barakat syndrome; Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Cancer Center

Study Record Dates

• First Submitted: July 13, 2024
• First Posted: July 24, 2024
• Study Start: September 1, 2023
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: July 24, 2024

Record last verified: 2024-07

Locations

CN (1)