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

NCT ID: NCT06518018

Last Updated: 2024-07-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-09-01
• Study Completion Date: 2025-09-01

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.

Detailed Description

Study Title: Exploring the Efficacy and Safety of High-Dose Rate Brachytherapy Combined with Immunotherapy and Chemotherapy as a Second-Line Treatment in Patients with Advanced Non-Small Cell Lung Cancer

Background:

Non-small cell lung cancer (NSCLC) is a significant health concern in China, accounting for approximately 18.1% of new cancer cases in 2022. Despite advancements in targeted therapies and immunotherapies, patients with advanced NSCLC who progress after initial treatment face limited options and poor prognosis. This study aims to address this unmet clinical need by investigating a novel combination therapy.

Objectives:

Primary: To evaluate the objective response rate (ORR) of high-dose rate (HDR) brachytherapy combined with immune checkpoint inhibitors (ICIs) and chemotherapy in advanced NSCLC patients.

Secondary: To assess progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety of the combination therapy.

Study Design:

This is a single-center, retrospective, propensity score-matched study comparing two treatment approaches:

Study group: HDR brachytherapy + ICIs + chemotherapy Control group: ICIs + chemotherapy alone

Treatment Protocol:

Study group: Patients will receive HDR brachytherapy (30Gy single fraction), followed by pembrolizumab and docetaxel chemotherapy within 1-3 days.

Control group: Patients will receive pembrolizumab and docetaxel chemotherapy without brachytherapy.

Key Scientific Questions:

Evaluate the potential improvement in second-line treatment efficacy for advanced NSCLC patients through the combination therapy.

Investigate the mechanisms by which HDR brachytherapy enhances the effectiveness of ICIs and chemotherapy.

Analyze the differential efficacy of the combination therapy across various subgroups of NSCLC patients.

Rationale:

Recent evidence suggests that radiotherapy can exert immunomodulatory effects, potentially enhancing immune treatment responses. High-dose radiotherapy has been shown to improve local control and survival rates in early-stage NSCLC when combined with immunotherapy. This study extends this concept to advanced NSCLC as a second-line treatment option.

Significance:

This research addresses a critical gap in current treatment options for advanced NSCLC patients who have progressed after immunotherapy. It aims to:

Improve patient outcomes in terms of quality of life and survival. Advance scientific understanding of the interaction between radiotherapy and immunotherapy.

Explore potential biomarkers for treatment response prediction. Contribute to the development of more personalized treatment strategies in oncology.

Innovation:

This is the first study to investigate HDR brachytherapy combined with ICIs and chemotherapy for previously treated advanced NSCLC patients. The novel combination strategy shows potential for improved efficacy and safety, offering new options for second-line treatment of advanced NSCLC.

Expected Outcomes:

The study aims to demonstrate improved ORR, PFS, and OS in the combination therapy group compared to the control group. It also seeks to establish the safety profile of the combination therapy and identify patient subgroups that may benefit most from this approach.

Conclusion:

This study represents a significant step towards addressing the unmet needs of advanced NSCLC patients who have progressed after initial treatment. By exploring this innovative combination therapy, the research aims to contribute valuable insights to the field of oncology and potentially improve treatment outcomes for this challenging patient population.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Study Group

HDR Brachytherapy + Immunotherapy + Chemotherapy Group

HDR brachytherapy (30Gy single fraction)

Intervention Type: 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.

Control Group

Immunotherapy + Chemotherapy Group

Immunotherapy

Intervention Type: 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

Interventions

HDR brachytherapy (30Gy single fraction)

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.

Intervention Type: RADIATION

Immunotherapy

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

Intervention Type: DRUG

Other Intervention Names

ICIs; chemotherapy; chemotherapy

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First People's Hospital of Neijiang

OTHER

Sponsor Role: lead

Responsible Party

Ou Jiang

Chief of Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Second People's Hospital of Neijiang

Neijiang, Sichuan, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 30093664 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33891980 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28094262 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25754329 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35906199 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34970277 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30619280 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29945993 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28577836 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35980349 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25799953 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31154919 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35108059 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33872070 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30642458 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35143424 (View on PubMed)

Other Identifiers

lunshen（yan）2023.no 10

Identifier Type: -

Identifier Source: org_study_id