Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT06501378

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

Led by Fudan University · Updated on 2024-08-28

40

Participants Needed

1

Research Sites

52 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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. Though most of the current studies excluded patients with active BM, we believe that these patients need more attention. In this trial, we focus on patients with active BM and treat them with PD-1/PD-L1 inhibitor, chemotherapy and SRT/WBRT.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18 years or older
  • Karnofsky Performance Status (KPS) score of 70 or higher
  • Negative genetic tests for EGFR, ALK, and ROS-1 driver genes
  • Pathological confirmation of non-small cell lung cancer
  • Clinical stage IV disease according to AJCC 8th edition (2017)
  • Diagnosed with brain metastasis at diagnosis, with at least one brain lesion larger than 5mm on thin-section MRI
  • Active brain metastases not controlled by symptomatic treatments like mannitol or dexamethasone
  • Completed baseline assessment including enhanced brain MRI before treatment
  • Provided informed consent to participate
Not Eligible

You will not qualify if you...

  • Presence of multiple primary or metastatic tumors except treated early skin cancer or cervical carcinoma in situ without recurrence for over 5 years
  • Severe autoimmune diseases such as active inflammatory bowel disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, or autoimmune vasculitis
  • Unsuitability for brain MRI or stereotactic brain radiotherapy as judged by researchers
  • Positive mutations in EGFR, ALK, or ROS1 genes
  • Uncontrolled epilepsy, central nervous system disease, or mental disorders affecting consent or compliance
  • Symptomatic interstitial lung disease or active infection/non-infectious pneumonia
  • Risk factors for intestinal perforation including active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or abdominal cancer
  • Active infection, heart failure, recent myocardial infarction within 6 months, unstable angina, or unstable arrhythmia
  • Other uncontrolled diseases or clinical findings that may interfere with results or increase treatment risks
  • Presence of small cell lung cancer components
  • Pregnancy or breastfeeding
  • Immunodeficiency diseases including HIV, history of organ or stem cell transplantation
  • Known hepatitis B or C, or active pulmonary tuberculosis infection
  • Receipt of tumor vaccines or other vaccines (except seasonal influenza) within 4 weeks before treatment start
  • Concurrent use of other immunomodulators, chemotherapy drugs, experimental drugs, or long-term corticosteroids
  • Allergy or contraindication to PD-1/PD-L1 inhibitors or chemotherapy drugs

AI-Screening

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Trial Site Locations

Total: 1 location

1

Fudan University Shanghai Cancer Center

Shanghai, China

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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