Prophylactic Cranial Irradiation Versus Observation in Stage IV NSCLC Randomized Controlled Clinical Study

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Primary Purpose

Status

Recruiting

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Prophylactic Cranial Irradiation for experiment arm

About this trial

This is an interventional treatment trial for Prophylactic Cranial Irradiation, Cumulative Incidence of Brain Metastases focused on measuring stage IV non-small cell lung cancer, PCI

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with pathologically or cytologically confirmed NSCLC; patients with clinical stage IV and no brain metastases [AJCC 8th edition]; no previous treatment Age 18 ~ 80 years old, body condition score ECOG 0 ~ 2 or KPS≥70; No contraindications such as radiotherapy, EGFR-TKI, chemotherapy, or immunotherapy; IMRT is required for primary tumor radiotherapy. DT: 60-70Gy Metastases are treated with three-dimensional radiotherapy (IMRT/SRT/SBRT/VMAT, etc.) and large segmentation radiotherapy. The subject must have no major organ dysfunction or laboratory tests that meet the following requirements: Hematological tests such as liver and kidney function were in the normal range of laboratory standards; Cardiac function: electrocardiogram excluded organic arrhythmia; Pulmonary function test: FEV1>50%, mild-moderate lung function limited. Signed informed consent before treatment (radiotherapy, chemotherapy, immunization, targeted drug therapy); The patient had good compliance with the treatment and follow-up received. Exclusion Criteria: Patients with brain metastasis; Stage IV NSCLC patients with malignant pleural effusion, pericardial effusion and other serous effusion; Patients with extensive liver metastasis and intrapulmonary metastasis that have seriously affected liver and lung function; Patients with uncontrolled hypertension, diabetes, unstable angina, history of myocardial infarction, or symptomatic congestive heart failure or uncontrolled arrhythmia within the past 12 months; Have a clinically clear diagnosis of heart valve disease; The disease active phase of bacterial, fungal, or viral infection; Mental disorders; Severe impaired lung function; Pregnant or lactating patients; Patients with a history of active malignancy other than small cell lung cancer prior to enrollment; Non-melanoma skin basal cell carcinoma, in situ cervical cancer, cured early prostate cancer excepted; Patients with an allergy and known or suspected allergy to any investigational drug for which no alternative medicine is available; Patients with poor compliance; Researchers consider it inappropriate to participate in this experiment.

Sites / Locations

Guizhou Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

PCI arm

observation arm

Arm Description

72 stage IV NSCLC patients were randomly enrolled in the group. And all required to have a baseline negative MRI scan for central nervous system (CNS) disease. For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor. Imaging reexamination 2 months after TKI treatment confirmed the efficacy of CR, PR, and SD; meanwhile, reexamination of head MR Examination confirmed no intracranial metastasis, and PCI was performed DT 30Gy/10f. For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. PCI DT: 30Gy/10f.Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.

72 stage IV NSCLC enrolled in the observation group. And all required to have a baseline negative magnetic resonance imaging (MRI) scan for central nervous system (CNS) disease. For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor. For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. then observation. Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.

Outcomes

Primary Outcome Measures

PFS is defined as the duration of time from start of treatment to time of progression or death,whichever occurs first.,CBM is defined as cumulative incidence of brain metastases.

Secondary Outcome Measures

Overall survival is defined as the time interval from date of diagnosis to date of death from any cause. Quality of life and neurocognitive function.

Full Information

NCT ID

NCT06014450

First Posted

August 8, 2023

Last Updated

August 23, 2023

Sponsor

Guizhou Medical University

1. Study Identification

Unique Protocol Identification Number

NCT06014450

Brief Title

Prophylactic Cranial Irradiation Versus Observation in Stage IV NSCLC Randomized Controlled Clinical Study

Official Title

Department of Oncology, Affiliated Hospital of Guizhou Medical University Affiliated Cancer Hospital of Guizhou Medical University

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 1, 2023 (Anticipated)

Primary Completion Date

August 1, 2025 (Anticipated)

Study Completion Date

August 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Guizhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

Brief Summary

Lung cancer has remained the leading cause of cancer-related deaths worldwide. An important and frequent cause of morbidity in this patient group is the development of brain metastases (BM). Lung cancer represents the leading cause of BM, and previous reports have shown that approximately 40% of patients will develop BM throughout their disease. Additionally, due to the improved use of advanced imaging techniques as part of routine initial staging. Another factor to consider is the considerably prolonged survival in patients with lung cancer as a direct result of the medical advances that have improved systemic disease control in the past 2 decades. The development of BM has recognized as one of the most detrimental factors for patient prognosis, with a negative impact on quality of life (QoL), concomitant neurocognitive disorders, and, importantly, a significant decrease in OS. RTOG 0214 shows that In patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM. NVALT-11/DLCRG-02 Study shows that PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase in low-grade toxicity. In conclusion, PCI improved DFS and decreased the risk of BM in patients with LA-NSCLC.Recent studies suggest NSCLC, including stage IV NSCLC, PCI significantly decreased CBM in addition to increasing progression-free survival and OS. At present, few studies on whether prophylactic radiation therapy can reduce the rate of brain metastasis and OS in stage IV NSCLC. In this randomized controlled study of stage IV NSCLC, we investigated whether PCI reduces the chance of brain metastases and whether it has a survival benefit.

Detailed Description

Group sample sizes of 72 in Group 1 and 72 in Group 2 achieve 90.140% power to detect a difference between the group proportions of 0.3100. The Group 2 proportion is 0.0700. The Group 1 proportion is assumed to be 0.1700 under the null hypothesis and 0.3800 under the alternative hypothesis. The test statistic used is the one-sided Z test (unpooled). The significance level of the test is 0.0250. For all patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor. Imaging reexamination 2 months after TKI treatment confirmed the efficacy of CR, PR, and SD; meanwhile, reexamination of head MR Examination confirmed no intracranial metastasis. For all patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. Then,for the experiment arm,patients will receive prophylactic cranial irradiation DT: 30Gy/10f. Followed systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years. For the observation arm,without prophylactic cranial irradiation,Followed systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years. The primary end point was incidence of brain metastases（CBM）, PFS, and the secondary end point was OS、quality of life (QoL), concomitant neurocognitive disorders。

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prophylactic Cranial Irradiation, Cumulative Incidence of Brain Metastases

Keywords

stage IV non-small cell lung cancer, PCI

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

144 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

PCI arm

Arm Type

Experimental

Arm Description

72 stage IV NSCLC patients were randomly enrolled in the group. And all required to have a baseline negative MRI scan for central nervous system (CNS) disease. For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor. Imaging reexamination 2 months after TKI treatment confirmed the efficacy of CR, PR, and SD; meanwhile, reexamination of head MR Examination confirmed no intracranial metastasis, and PCI was performed DT 30Gy/10f. For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. PCI DT: 30Gy/10f.Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.

Arm Title

observation arm

Arm Type

Placebo Comparator

Arm Description

72 stage IV NSCLC enrolled in the observation group. And all required to have a baseline negative magnetic resonance imaging (MRI) scan for central nervous system (CNS) disease. For patients with positive TKI detection, TKI combined with concurrent radiotherapy DT60-70Gy for the primary tumor. For patients with negative TKI detection, the treatment mode was platinum-based regimen chemotherapy combined with concurrent radiotherapy for DT60-70Gy for the primary tumor. Imaging reexamination after 2 cycles of chemotherapy confirmed the efficacy of CR, PR, and SD, and skull MR Examination confirmed that there was no intracranial metastasis. then observation. Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.

Intervention Type

Radiation

Intervention Name(s)

Prophylactic Cranial Irradiation for experiment arm

Intervention Description

Prophylactic Cranial Irradiation DT30Gy/10f

Primary Outcome Measure Information:

Title

PFS is defined as the duration of time from start of treatment to time of progression or death,whichever occurs first.,CBM is defined as cumulative incidence of brain metastases.

Time Frame

Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.

Secondary Outcome Measure Information:

Title

Overall survival is defined as the time interval from date of diagnosis to date of death from any cause. Quality of life and neurocognitive function.

Time Frame

Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Patients with pathologically or cytologically confirmed NSCLC; patients with clinical stage IV and no brain metastases [AJCC 8th edition]; no previous treatment Age 18 ~ 80 years old, body condition score ECOG 0 ~ 2 or KPS≥70; No contraindications such as radiotherapy, EGFR-TKI, chemotherapy, or immunotherapy; IMRT is required for primary tumor radiotherapy. DT: 60-70Gy Metastases are treated with three-dimensional radiotherapy (IMRT/SRT/SBRT/VMAT, etc.) and large segmentation radiotherapy. The subject must have no major organ dysfunction or laboratory tests that meet the following requirements: Hematological tests such as liver and kidney function were in the normal range of laboratory standards; Cardiac function: electrocardiogram excluded organic arrhythmia; Pulmonary function test: FEV1>50%, mild-moderate lung function limited. Signed informed consent before treatment (radiotherapy, chemotherapy, immunization, targeted drug therapy); The patient had good compliance with the treatment and follow-up received. Exclusion Criteria: Patients with brain metastasis; Stage IV NSCLC patients with malignant pleural effusion, pericardial effusion and other serous effusion; Patients with extensive liver metastasis and intrapulmonary metastasis that have seriously affected liver and lung function; Patients with uncontrolled hypertension, diabetes, unstable angina, history of myocardial infarction, or symptomatic congestive heart failure or uncontrolled arrhythmia within the past 12 months; Have a clinically clear diagnosis of heart valve disease; The disease active phase of bacterial, fungal, or viral infection; Mental disorders; Severe impaired lung function; Pregnant or lactating patients; Patients with a history of active malignancy other than small cell lung cancer prior to enrollment; Non-melanoma skin basal cell carcinoma, in situ cervical cancer, cured early prostate cancer excepted; Patients with an allergy and known or suspected allergy to any investigational drug for which no alternative medicine is available; Patients with poor compliance; Researchers consider it inappropriate to participate in this experiment.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Bing Lu, Bachelor

Phone

13809432527

Email

lbgymaaaa@163.com

Facility Information:

Facility Name

Guizhou Cancer Hospital

City

Guiyang

State/Province

Guizhou

ZIP/Postal Code

550004

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lu Bing, MD

Phone

86-13765066737

Email

574679514@qq.com

12. IPD Sharing Statement

Plan to Share IPD

No

Prophylactic Cranial Irradiation, Cumulative Incidence of Brain Metastases

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial