PCI and Brain MRI Follow-up vs Brain MRI Follow-up Alone in Limited-stage SCLC Patients

Prophylactic Cranial Irradiation and Brain MRI Follow-up Versus Brain MRI Follow-up Alone in Patients With Limited-stage Small Cell Lung Cancer Who Achieved Complete Remission After Definitive Radio-chemotherapy: a Prospective Randomized Trial

At present, prophylactic cranial irradiation (PCI) is part of standard care for patients with limited-stage small cell lung cancer (SCLC) who have achieved good response after definitive thoracic radiotherapy and chemotherapy. However, the value of PCI is being challenged in the era when MRI examination of brain has been popularized.

The goal of this clinical study is to compare PCI and regular brain MRI follow-up (control arm) and regular brain MRI follow-up alone (study arm) in patients with limited-stage SCLC who have received definitive radiotherapy and chemotherapy and acheived complete remission (CR) of tumor.

The main questions to answer are:

1. Whether the 2-year brain metastasis-free survival rate of the study group is not inferior to that of the control group.
2. The difference of 2-year overall survival rate between the control group and the study group.
3. Whether the patients in the study group have better overall quality of life than those in the control group.

Participants will randomly receive either PCI and regular brain MRI follow-up or regular brain MRI follow-up alone.

Study Overview

• Status: Recruiting
• Conditions: Small Cell Lung Cancer Limited Stage
• Intervention / Treatment: Radiation: Prophylactic cranial irradiation; Radiation: Thoracic radiotherapy; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiao Hu, MD, PhD; Phone Number: +86-571-88128172; Email: huxiao@zjcc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University, Cancer Center
      • Contact: Ming Chen, MD.PhD.
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Xiao Hu, MD. PhD.; Phone Number: +86-571-88128172; Email: huxiao@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically/cytologically proven diagnosis of SCLC.
• Age ≥ 18 years.
• Karnofsky performance status ( KPS) ≥80.
• The limited-stage is defined as the tumor confined to one side of the chest, including ipsilateral hilar, bilateral mediastinum, and bilateral supraclavicular lymph nodes. (The definition of metastatic lymph nodes is that the short diameter ≥ 1cm or PET-CT shows increased metabolism with SUV≥2.5, or proved by mediastinoscopy/EBUS/TBNA biopsy. The thickness of pleural effusion on chest CT is less than 1cm (unless cytology proves to be malignant pleural effusion). According to 8th AJCC/UICC TNM staging system, it is the I-IIIC without intrapulmonary metastasis.
• Patients who have received definitive chest radiotherapy and chemotherapy and achieved complete remission of tumor within 4-6 weeks after the end of radio-chemotherapy (in accordance with the Response Evaluation Criteria in Solid Tumors v.1.1 including enhanced CT scan of chest and abdomen, enhanced brain MRI, bone scan and tumor markers).
• Good follow-up compliance;
• Fully understand this study, and voluntarily sign the informed consent form.

Exclusion Criteria:

• Patients with a history of malignant tumors (past or concurrent) within 5 years, excluding papillary thyroid cancer, non-malignant melanoma skin cancer and cervical carcinoma in situ.
• Patients who have received radical surgery (excluding biopsy).
• Patients with psychiatric history, pregnancy and lactation.
• Uncontrolled diabetes, hypertension, severe active infection.
• Patients with chronic diseases of central nervous system.
• Patients with contraindications of brain MRI examination.
• Other situations deemed unsuitable by the doctor in charge.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm; Patients who are randomized to control arm are those who have achieved complete remission of tumor after definitive radio-chemotherapy and will receive PCI and regular brain MRI follow-up.	Radiation: Prophylactic cranial irradiation; Prophylactic cranial irradiation (PCI) is actually a habitual statement. It is a technique used to eliminate tiny metastatic lesions that have already existed in the brain, but can not be found by brain MRI and other inspection methods.; Radiation: Thoracic radiotherapy; Thoracic radiotherapy is a local treatment of tumors located in the chest using ionizing radiation.; Drug: Chemotherapy; Chemotherapy is the abbreviation of chemical drug therapy. It is a treatment method that uses chemical drugs to prevent the proliferation, invasion and metastasis of cancer cells, and finally kill cancer cells.
Experimental: Study arm; Patients who are randomized to study arm are those who have achieved complete remission of tumor after definitive radio-chemotherapy and will receive regular brain MRI follow-up alone.	Radiation: Thoracic radiotherapy; Thoracic radiotherapy is a local treatment of tumors located in the chest using ionizing radiation.; Drug: Chemotherapy; Chemotherapy is the abbreviation of chemical drug therapy. It is a treatment method that uses chemical drugs to prevent the proliferation, invasion and metastasis of cancer cells, and finally kill cancer cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year brain metastasis-free survival estimated with kaplan-Meier method	To test with a one-sided significance of 5% whether for the treatment of limited-stage SCLC patients, brain MRI follow-up alone is non-inferior in terms of 2-year brain metastasis-free survival compared to PCI and brain MRI follow-up. Participants were monitored for up to 2 years. The brain metastasis-free survival time is defined as the time between the date of the first treatment until the date of first documented diagnosis of brain metastasis or the date of death from any cause.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year overall survival estimated with kaplan-Meier method	To compare 2-year overall survival between patients who receive brain MRI follow-up alone and those who receive both PCI and brain MRI follow-up, with kaplan-Meier estimates. Participants were monitored for up to 2 years. The overall survival time is defined as the time between the date of the first treatment until the date of death from any cause.	Up to 2 years
Intra-cranial progressive patterns	To compare the intra-cranial progressive patterns between patients who receive brain MRI follow-up alone and those who receive both PCI and brain MRI follow-up within 2 years. Intra-cranial progression is evaluated via the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. In this study, Intra-cranial progressive disease is defined as the new lesions developed in the brain.	Up to 2 years

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Collaborators: Sun Yat-sen University; First Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Xiao Hu, MD, PhD, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 16, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: prognosis; prophylactic cranial irradiation; brain MRI follow-up
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: PCI+MRI vs. MRI

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