Health TrialsbyHealthPanel

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

ConditionsNSCLC Stage IVBrain Metastases
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFudan University

About this trial

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) .

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial design

Design model

Parallel

Treatments tested in this trial

  • PD-L1/PD-1 inhibitor and chemotherapy

    Drug

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

  • 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.

Treatment groups

54 Participants
are divided into 2 treatment groups
Group A: stable BM, PD-1/PD-L1 inhibitors plus chemotherapyActive comparator 1 intervention
Group B: stable BM, PD-1/PD-L1 inhibitors, chemotherapy plus radiotherapyExperimental treatment 2 interventions

Trial outcomes

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.

Time frame
2 years

Secondary outcomes

1

Intracranial Progression-Free Survival (iPFS)

The time from the start of treatment when the patient is enrolled until the observation of intracranial disease progression (appearance of new lesions, enlargement of existing lesions, excluding the possibility of pseudo-progression such as radiation necrosis) or death from any cause. Patients who have not progressed at the time of analysis will have their last contact date used as the cutoff date.

Time frame
2 years
2

Intracranial Objective Response Rate (iORR)

The percentage of participants in the analysis population whose brain lesions achieve CR or PR, assessed according to the modified RECIST 1.1 criteria.

Time frame
2 years
3

Progression-Free Survival (PFS)

The time from the start of treatment until the observation of disease progression or death from any cause, assessed according to the RECIST 1.1 criteria. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.

Time frame
2 years
4

Overall Survival (OS)

The time from the start of treatment until death from any cause. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.

Time frame
2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fudan University

Lead sponsor

Source ClinicalTrials.gov
Apply now