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

August 23, 2023 updated by: Bing Lu, Guizhou Medical University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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。

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
144

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guizhou
      • Guiyang, Guizhou, China, 550004
        • Recruiting
        • Guizhou Cancer Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PCI arm

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.
Radiation: Prophylactic Cranial Irradiation for experiment arm
Prophylactic Cranial Irradiation DT30Gy/10f
Placebo Comparator: observation arm

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.
Radiation: Prophylactic Cranial Irradiation for experiment arm
Prophylactic Cranial Irradiation DT30Gy/10f

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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.
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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.
Systematic imaging examinations in the first month following systemic treatment, every 3 months in 2 years, and every 6 months in 5 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guizhou Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 8, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 28, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PCI for stage IV NSCLC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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