Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Stable Brain Metastasis

NCT06501391 | Recruiting Phase 2

• 1 other identifier: 2024Lung-PD1-stable BM
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. However, recent advancements with immune checkpoint inhibitors (ICIs) have shown promise, with some studies reporting improved intracranial objective response rates, progression-free survival, and overall survival when combined with chemotherapy. Despite these improvements, challenges remain, such as treatment resistance, recurrence, and the need for better therapeutic strategies. Local interventions like stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) have been crucial for treating BM, with SRT being particularly effective. The combination of immunotherapy and radiotherapy is emerging as a synergistic approach, with studies suggesting it may enhance local control and survival rates while maintaining safety. Guidelines recommend SRT for patients with limited BMs, and clinical data support the safety and efficacy of combining brain radiotherapy with immunotherapy. A meta-analysis and other studies have shown promising results with this combination, including local control rates and overall survival benefits, with manageable toxicities. However, there is still a need for more prospective clinical trials to verify the safety and efficacy of combining cranial radiotherapy with immunotherapy in NSCLC patients with BM, especially those without driver gene mutations. Therefore, we plan to conduct a phase 2 prospective study, focusing on combining brain radiotherapy with PD-1/PD-L1 inhibitors. We will stratify eligible patients based on the status of BMs (active BM vs stable BM) .

Conditions

NSCLC Stage IV; Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) after treatment, assessed according to the RECIST 1.1 criteria.

  2 years

Secondary Outcomes (5)

• Intracranial Progression-Free Survival (iPFS)

  2 years

• Intracranial Objective Response Rate (iORR)

  2 years

• Progression-Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

• Treatment-Related Adverse Event (TRAE)

  2 years

Study Arms (2)

stable BM, PD-1/PD-L1 inhibitors plus chemotherapy

ACTIVE COMPARATOR

Drug: PD-L1/PD-1 inhibitor and chemotherapy

stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapy

EXPERIMENTAL

Drug: PD-L1/PD-1 inhibitor and chemotherapy; Radiation: SRT or WBRT

Interventions

PD-L1/PD-1 inhibitor and chemotherapy DRUG

Stable brain metastases patients in this arm will receive PD-L1/PD-1 inhibitors and chemotherapy.

stable BM, PD-1/PD-L1 inhibitors plus chemotherapy; stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapy

SRT or WBRT RADIATION

Stable brain metastases (BM) patients in this arm will receive stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) according to their BM condition.

stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• KPS score ≥ 70;
• Negative genetic testing for common driver genes including EGFR, ALK, ROS-1;
• Pathologically confirmed non-small cell lung cancer;
• Clinical stage IV (AJCC, 8th edition, 2017);
• Diagnosed with brain metastasis at the time of diagnosis, with at least one lesion in the brain with a diameter greater than 5mm on thin-section brain MRI;
• Complete baseline assessment of systemic lesions before treatment, including enhanced brain MRI;
• Informed consent from the patient.

You may not qualify if:

• Multiple primary or metastatic tumors (except early skin cancer, cervical carcinoma in situ that has been treated radically, with no recurrence or progression for more than 5 years);
• 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.;
• Patients judged by the researcher as unsuitable for brain MRI or stereotactic brain radiotherapy;
• EGFR, ALK, or ROS1 gene mutations;
• Active BMs that could not be controlled by symptomatic treatment, such as mannitol and dexamethasone
• Uncontrolled epilepsy, central nervous system disease, or history of mental disorders, judged by the researcher to potentially interfere with the signing of the informed consent form or affect patient compliance;
• Symptomatic interstitial lung disease or active infection/non-infectious pneumonia;
• Patients with risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation;
• Patients with active infection, heart failure, myocardial infarction within 6 months, unstable angina, or unstable arrhythmia;
• Other uncontrollable diseases or findings from physical examination or clinical experiments judged by the researcher to potentially interfere with the results or increase the risk of treatment complications for the patient;
• Mixed with small cell lung cancer components;
• Pregnant or lactating women;
• Congenital or acquired immunodeficiency diseases including HIV, or history of organ transplantation, allogeneic stem cell transplantation;
• Known HBV, HCV, active pulmonary tuberculosis infection;
• Patients who have received tumor vaccines, or have been vaccinated with other vaccines within 4 weeks before starting treatment (Note: Seasonal influenza vaccines are usually inactivated vaccines and are allowed, while nasal preparations are usually attenuated live vaccines and are not allowed);

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 15, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 28, 2024

Record last verified: 2024-08

Locations

CN (1)