Hippocampus-protective Synchronous Progressive Whole Brain Radiotherapy Combined With Osimertinib for Symptomatic Brain Metastases in Advanced EGFR-Mutated Non-Small Cell Lung Cancer: A Prospective Phase II Multicenter Single-Arm Clinical Study

Plain English Summary

Hippocampus-Protective Radiotherapy Combined With Osimertinib for Symptomatic Brain Metastases in EGFR-Mutated Lung Cancer is a Phase 2 clinical trial sponsored by Tianjin Medical University Cancer Institute and Hospital studying Naive Advanced Non-small Cell Lung Cancer With EGFR-sensitive Mutations (EGFR Exon 19 Deletion and Exon 21 L858R Mutation) and Symptomatic Brain Metastases. This trial tests a new approach combining a specialized form of radiation therapy with a targeted drug (osimertinib) for lung cancer that has spread to the brain. It is for patients with a specific type of non-small cell lung cancer (NSCLC) that has EGFR mutations and has caused symptoms in the brain. Participants will receive radiation to the brain and take osimertinib daily. They will have regular check-ups and scans to monitor their condition. Currently, standard treatments for brain metastases in this type of lung cancer may include surgery, radiation, or other targeted therapies, but this trial aims to improve outcomes and protect brain function. The trial aims to enroll 74 participants.

Official Summary

This is a single-arm, multicenter, open-label, phase Ⅱ exploratory clinical study, which plans to enroll 74 treatment-naive patients with EGFR-sensitive mutations (exon 19 deletion, exon 21 L858R mutation) and symptomatic brain metastases from non-small cell lung cancer (NSCLC). The primary objective is to evaluate the intracranial progression-free survival (iPFS) of hippocampal-sparing whole-brain radiotherapy (PTV: 20Gy/10 fractions) combined with simultaneous integrated boost to brain metastases (PGTV: 40Gy/10 fractions) plus osimertinib (80mg orally once daily). The secondary objectives are to assess efficacy indicators including overall progression-free survival (PFS), intracranial/systemic objective response rate (ORR), as well as safety. The primary endpoint is iPFS, supplemented by secondary endpoints such as PFS, ORR, disease control rate (DCR), overall survival (OS), adverse events (AE) evaluated per NCI-CTCAE v5.0 criteria, and neurocognitive function scores (MMSE/HVLT-R). By optimizing the combined mode of radiotherapy and targeted therapy, this study aims to provide a safer and more effective treatment option for such patients, balancing tumor control and quality of life protection.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18-75 with non-small cell lung adenocarcinoma and specific EGFR mutations (exon 19 deletion or exon 21 L858R mutation). Must have symptomatic brain metastases confirmed by imaging, with 1-10 lesions requiring treatment, and at least one measurable lesion. Cannot have received prior cancer treatment for NSCLC and must have good general health with adequate organ function. Patients with uncontrollable fluid buildup in body cavities or severe underlying diseases may not be eligible. This trial is studying Naive Advanced Non-small Cell Lung Cancer With EGFR-sensitive Mutations (EGFR Exon 19 Deletion and Exon 21 L858R Mutation) and Symptomatic Brain Metastases, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see how long patients live without their brain tumors growing or spreading after treatment, which means the treatment is working to control the cancer in the brain. The specific primary outcome measures are: Intracranial progression-free survival (iPFS ) (36 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for more effective and brain-sparing treatments for lung cancer that has spread to the brain, aiming to improve survival and quality of life. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Naive Advanced Non-small Cell Lung Cancer With EGFR-sensitive Mutations (EGFR Exon 19 Deletion and Exon 21 L858R Mutation) and Symptomatic Brain Metastases, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in advanced lung cancer, potentially improving treatment options and market share for EGFR-targeted therapies and advanced radiation techniques. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific radiation technique used (hippocampus-protective) and how it aims to minimize side effects on memory. Understand the daily schedule for taking osimertinib and the frequency of clinic visits, scans, and potential side effect monitoring. Be prepared for regular assessments of your neurological function and overall well-being throughout the study. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 74 participants

Interventions

• OTHER: Hippocampal-Sparing Whole-Brain Radiotherapy + Simultaneous Integrated Boost to Brain Metastases + O — Hippocampal-Sparing Whole-Brain Radiotherapy + Simultaneous Integrated Boost to Brain Metastases + O
• DRUG: Hippocampus-Protective Radiotherapy Combined With Osimertinib for Symptomatic Brain Metastases in EGFR-classic Mutated Lung Cancer — Hippocampus-Protective Radiotherapy Combined With Osimertinib for Symptomatic Brain Metastases in EGFR-classic Mutated Lung Cancer

Primary Outcomes

• Intracranial progression-free survival (iPFS ) (36 months)

Secondary Outcomes

• Overall survival (OS) (36 months)

Full Eligibility Criteria

Inclusion Criteria:

* Signed a written informed consent form prior to enrollment;
* Aged 18-75 years;
* Histopathologically confirmed non-small cell lung adenocarcinoma (NSCLC); EGFR gene test confirmed EGFR sensitive mutations, including exon 19 deletion (19del) and exon 21 L858R mutation (verified and confirmed by investigators at the respective study centers);
* Brain metastasis confirmed by contrast-enhanced cranial CT/MRI; the number of brain metastatic lesions requiring local dose escalation is 1-10, with at least one measurable intracranial lesion having a diameter ≥10 mm; the distance between metastatic lesions and important cerebral functional areas meets radiotherapy-related requirements; at least one measurable lesion (per RECIST v1.1 criteria) confirmed by contrast-enhanced extracranial CT/PET-CT;
* Symptomatic brain metastasis;
* ECOG performance status score: 0-2;
* Expected survival time of no less than 12 weeks;
* No prior anti-tumor treatment received for NSCLC;
* Normal function of vital organs, meeting the following requirements (no blood components or cell growth factors administered within 14 days):

A) Routine blood test criteria: Hb ≥100 g/L; ANC ≥1.5×10⁹/L; PLT ≥75×10⁹/L; B) Biochemical test criteria: TBIL ≤1.5×ULN (upper limit of normal); ALT and AST ≤2.5×ULN (for patients with liver metastasis, ALT and AST ≤5×ULN); serum creatinine ≤1.5×ULN, creatinine clearance rate ≥50 ml/min (calculated based on the Cockroft-Gault formula); C) Coagulation function criteria: INR ≤1.5×ULN and APTT ≤1.5×ULN; D) Cardiac color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥50%;

\- For non-surgically sterilized patients or women of childbearing potential: a medically approved contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) must be used during the study treatment period and for 3 months after the end of study treatment; non-surgically sterilized women of childbearing potential must have a negative serum or urine HCG test within 7 days prior to study enrollment, and must not be breastfeeding.

All subjects voluntarily participate in the study, with good compliance and willingness to cooperate with safety and overall survival follow-up.

Exclusion Criteria:

* Presence of uncontrollable third space effusion (e.g., pleural effusion, ascites) that cannot be managed with drainage or other interventions;
* Presence of multiple factors impairing oral drug administration and absorption (e.g., inability to swallow, post-gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.);
* Patients who are known to be pregnant, planning pregnancy, or women of childbearing potential who refuse to adopt effective contraceptive measures throughout the study period;
* Patients with severe concomitant diseases or those deemed ineligible for enrollment by the investigator;
* Patients with meningeal metastasis;
* Participation in other drug clinical trials within 4 weeks prior to enrollment;
* Concurrent receipt of other anti-tumor therapies;
* A known history of psychotropic drug abuse, alcoholism, or drug addiction in the subject;
* Underlying diseases that may interfere with study drugs (e.g., clinically significant electrocardiographic abnormalities, active interstitial lung disease);
* Any other conditions deemed by the investigator to potentially harm the subject or render them unable to meet or comply with the study requirements.

Trial Locations

• Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer (NSCLC)
• EGFR-Mutated Lung Cancer
• Brain Metastases
• Lung Adenocarcinoma
• Targeted Therapy
• Radiotherapy
• Oncology
• Cancer Treatment
• Neurological Oncology
• Thoracic Oncology

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