WBRT With Hippocampal-avoidance Technique Followed by SRT for Extensive-stage SCLC With Baseline Brain Metastases

A Phase I/II Study to Evaluate the Safety and Efficacy of Hippocampal-avoidance Whole Brain Radiotherapy Followed by Stereotactic Radiotherapy for Extensive-stage Small Cell Lung Cancer With Baseline Brain Metastases

This study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS as first-line treatment for SCLC patients with brain metastases.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases; SCLC,Extensive Stage
• Intervention / Treatment: Radiation: HA-WBRT plus SBRT

Detailed Description

At present, the standard treatment for SCLC brain metastases is whole brain radiotherapy (WBRT). However, WBRT is palliative in nature due to its low dose and poor long-term control rate of intracranial lesions. At the same time, with the advent of the era of immunotherapy, a variety of PD-1/PD-L1 monoclonal antibodies combined with chemotherapy have become the standard first-line treatment for extensive-stage SCLC(ES-SCLC). Studies have shown that the survival time of SCLC patients with brain metastases is expected to be further prolonged in the era of chemotherapy and immunotherapy. Therefore, it is particularly important to further improve the control rate of intracranial lesions.

It has been confirmed in previous studies that WBRT combined with stereotactic radiotherapy for visible intracranial lesions (SRS/SRT) can effectively improve the control rate of intracranial lesions. However, most of the previous studies of WBRT combined with SRT for brain metastases did not include or only included a very small number of patients with SCLC. Studies on thoracic radiotherapy for limited-stage small cell lung cancer have found that an increase in radiotherapy dose can significantly improve the prognosis of patients with SCLC, which was previously considered to be highly radiosensitive. It is reasonable to think that SRS combined with WBRT for SCLC brain metastases may improve the prognosis of patients.

WBRT is known to cause severe cognitive impairment, which has also led to the reluctance of some patients to undergo WBRT. In the era of chemotherapy, the NRG-CC001 study showed that Hippocampal avoidance WBRT (HA-WBRT) could better protect the cognitive function of patients without affecting the prognosis of patients. The 2022 ASTRO guidelines have clearly recommended the use of hippocampal protection techniques in WBRT. Considering the lack of previous literature on the use of SRS combined with WBRT in SCLC patients in the chemo-immunotherapy era, The aim of this study is to adopt the dose fractionation of SRS combined with WBRT, which has been proven to be safe in the treatment of brain metastases from NSCLC, and to evaluate the safety of this treatment mode in SCLC patients with brain metastases receiving standard first-line chemoimmunotherapy.

In summary, this study aims to evaluate the safety and efficacy of hippocampal-sparing WBRT combined with SRS in the first-line treatment of SCLC patients with baseline brain metastases who are suitable for SRS treatment during the standard first-line chemotherapy combined with immunotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhengfei Zhu; Phone Number: +8618017312901; Email: fuscczzf@163.com
• Study Contact Backup: Name: Xiao Chu; Phone Number: +8618017317922; Email: chuxiao@sibs.ac.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhengfei Zhu, MD; Phone Number: +86-18017312901; Email: fuscczzf@163.com
    • Contact: Xiao Chu; Phone Number: +86-18017317922; Email: chuxiao@sibs.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Eastern Cooperative Oncology Group(ECOG) performance status score 0-2;
2. Small cell lung cancer confirmed by histopathology or cytology;
3. Complete baseline imaging data (including brain enhanced MRI/CT, positron emission tomography(PET/CT) or chest enhanced CT+ bone scan + neck and abdomen B ultrasound /CT) should be obtained before first-line treatment;
4. Patients with initial diagnosis of ES-SCLC with brain metastases who planned to receive at least 4 cycles of standard platinum-based doublet chemotherapy combined with immunotherapy (PD-1 or PD-L1 monoclonal antibody) as first-line treatment, and who met the organ function requirements as judged by the investigator;
5. Brain metastases assessed by contrast-enhanced MRI met the criteria for SRS (less than or equal to 10 brain metastases, maximum tumor volume less than 10ml, maximum tumor diameter less than 3cm, total tumor volume less than 15ml, and no evidence of leptomeningeal metastasis).
6. No history of other malignant tumors;
7. Male/female of childbearing age agreed to use contraception (surgical ligation or oral contraceptive/intrauterine device + condom) during the trial;
8. Life expectancy ≥3 months
9. Patients must be able to understand and voluntarily sign informed consent.

Exclusion Criteria:

1. Patients with non-small cell lung cancer (NSCLC) components on baseline pathological examination;
2. Patients who had received any antitumor therapy prior to ES-SCLC diagnosis;
3. Patients with imaging evidence of leptomeningeal metastasis or suspected leptomeningeal metastasis with symptoms and signs;
4. patients unable to undergo contrast-enhanced MRI;
5. Patients with severe symptoms of brain metastases requiring emergency surgery to reduce intracranial pressure;
6. Patients who could not complete immobilization for radiotherapy or tolerate radiotherapy;
7. Symptomatic interstitial lung disease or active infectious/noninfectious pneumonia;
8. Patients requiring long-term corticosteroid or immunosuppressive therapy;
9. Patients who are allergic to PD-1 or PD-L1 monoclonal antibody immunotherapy or unable to receive immune maintenance therapy for other reasons;
10. Lactating or pregnant women;
11. The patient had severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.
12. Medical examination or clinical findings or other uncontrollable conditions that the investigator considers may interfere with the results or increase the risk of treatment complications for the patient;
13. Patients with mental illness, substance abuse, or social problems that could affect adherence were excluded from enrollment after physician review.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HA-WBRT with SRS; hippocampal-sparing WBRT combined with SRS will be used to treat SCLC patients with baseline brain metastases during standard first-line chemotherapy combined with immunotherapy.	Radiation: HA-WBRT plus SBRT; hippocampal-avoidance whole brain radiotherapy (WBRT) followed by stereotactic body radiotherapy (SBRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dose-limiting toxicities rate	dose-limiting toxicities(DLTs) were assessed according to CTCAE 5.0 criteria and included the following three conditions, with the exception of asymptomatic biochemical abnormalities: (1) grade 3 toxicity lasting for more than 7 consecutive days; (2) Grade 4 toxicity excluding neutropenia and thrombocytopenia; (3) Treatment-related grade 5 adverse events could not be excluded.	30 days since the final day of radiotherapy
1-year intracranial progression-free survival rate	1-year intracranial progression-free survival (iPFS) rate was defined as proportion of patients without intracranial disease progression or death at 1 year of follow-up	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to intracranial progression	Time to intracranial progression was defined as the time from enrollment for treatment to the observation of progression of intracranial disease.	one year
Changes in learning and memory function	learning and memory function was assessed at 2, 4, 6, and 12 months from the first day of radiotherapy using the Hopkins Verbal Learning Test (HVLT-R)	one year
processing speed and executive function	processing speed and executive function was assessed at 2, 4, 6, and 12 months from the first day of radiotherapy using the trail making test (TMT-Part A, to assess processing speed, and TMT-Part B, to assess executive function).	one year
overall survival	overall survival(OS) was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.	one year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 24, 2024
• First Submitted That Met QC Criteria: February 3, 2024
• First Posted (Actual): February 5, 2024

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: stereotactic body radiotherapy (SBRT); whole brain radiotherapy (WBRT)
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: SCLC-BRT

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