A Study of Targeted Radiation Therapy in People With Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The purpose of this study is to see whether adding liver stereotactic ablative radiotherapy/L-SABR to standard drug therapy is better than standard drug therapy alone for people with metastatic non-small cell lung cancer/NSCLC.

Official Title
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A Phase II Trial of Hepatic Ablation of Metastases to Modulate and Enhance Immunotherapy Response (HAMMER) in NSCLC

Conditions
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Non Small Cell Lung Cancer, Non Small Cell Lung Cancer Metastatic, Non-small Cell Carcinoma, NSCLC, NSCLC Stage IV

Intervention / Treatment
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* Radiation: L-SABR
* Biological: Anti-PD-(L)1 based immunotherapy
* Drug: Platinum based chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be greater than 18 years of age on day of signing informed consent. Have a histologically confirmed diagnosis of stage IV NSCLC (includes patients who have progressed on durvalumab for Stage III NSCLC) without known mutations in epidermal sensitizing growth factor (EGFR) or BRAF or rearrangements in ALK (anaplastic lymphoma kinase) or ROS-1. Newly diagnosed metastatic non-small cell lung cancer (NSCLC), including both de novo and secondary metastatic disease, with liver metastases Plan to initiate standard of care anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy Have a performance status of 0-2 on the ECOG Performance Scale. Liver function tests: Total Bilirubin ≤ 1.5 x ULN AST/ ALT ≤ 5 x ULN Eligible for L- SABR to all liver metastases. Eligible for or plan to initiate standard of care therapy with anti-PD(L)-1 therapy alone or anti-PD(L)-1 therapy in combination with platinum-based chemotherapy, up to cycle 3. Patients with known HIV are eligible provided they are under treatment with effective anti-retroviral therapy with CD4 >200 cells/microliter ≤ 28 days prior to registration Exclusion Criteria: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included. Patients with prior external beam radiation therapy to the liver. Patients with known active Hepatitis B or Hepatitis C. Patients with immunosuppression including pharmacological immunosuppression with chronic steroids or immune modulators like cyclosporin or methotrexate and patients with active autoimmune disease. Patients who are pregnant or breastfeeding Men or women not using effective contraception.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-SABR Arm<br>Participants randomized to the experimental arm will continue with standard of care treatment but will also undergo radiation simulation for L-SABR/Liver Stereotactic Ablative Radiation Therapy. | Radiation: L-SABR<br>* L-SABR will be delivered in a week during which the patient receives no chemotherapy. L-SABR can be on the same week or even day as anti-PD-(L)1 therapy.<br>* Other names: Liver Stereotactic Ablative Radiation Therapy;Biological: Anti-PD-(L)1 based immunotherapy<br>* Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy<br>* Other names: Standard of Care;Drug: Platinum based chemotherapy<br>* Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy<br>* Other names: Standard of Care;|
| Active Comparator: Control Arm<br>Participants randomized to the control arm will be treated according to the standard of care. | Biological: Anti-PD-(L)1 based immunotherapy<br>* Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy<br>* Other names: Standard of Care;Drug: Platinum based chemotherapy<br>* Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy<br>* Other names: Standard of Care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median progression-free survival | Primary outcomes is to determine if L-SABR, when added to first line standard of care anti-PD-(L)1 based immunotherapy +/- chemotherapy, can improve median progression-free survival (PFS) in patients with metastatic NSCLC involving the liver. | up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non small cell lung cancer, Non Small Cell Lung Cancer Metastatic, Non-small Cell Carcinoma, liver stereotactic ablative radiotherapy, L-SABR, NSCLC, NSCLC Stage IV, Memorial Sloan Kettering Cancer Center, 22-368