Clinical trial NCT06518018: Efficacy and Safety of High-Dose Rate Brachytherapy with Immunotherapy and Chemotherapy As Second-Line Treatment for Advanced Non-Small Cell Lung Cancer
Official 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: a Single-Center, Retrospective, Propensity Score-Matched Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
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
Lead sponsor: The First People's Hospital of Neijiang
Sponsor class: OTHER
First posted: 2024-07-24
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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:
measure: Progression-Free Survival (PFS)
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: 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.
Locations:
city: Neijiang
country: China
facility: The Second People's Hospital of Neijiang
state: Sichuan
Study officials:
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