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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05657873

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

9.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Non Small Cell Lung Cancer Metastatic Non-small Cell Carcinoma NSCLC NSCLC Stage IV	Radiation: L-SABR Biological: Anti-PD-(L)1 based immunotherapy Drug: Platinum based chemotherapy	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

68 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 9, 2022

Anticipated Primary Completion Date :

Dec 9, 2025

Anticipated Study Completion Date :

Dec 9, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: L-SABR Arm 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 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. Other Names: Liver Stereotactic Ablative Radiation Therapy Biological: Anti-PD-(L)1 based immunotherapy Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy Other Names: Standard of Care Drug: Platinum based chemotherapy Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy Other Names: Standard of Care
Active Comparator: Control Arm Participants randomized to the control arm will be treated according to the standard of care.	Biological: Anti-PD-(L)1 based immunotherapy Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy Other Names: Standard of Care Drug: Platinum based chemotherapy Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy Other Names: Standard of Care

Arm

Intervention/Treatment

Experimental: L-SABR Arm

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

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.

Other Names:

Liver Stereotactic Ablative Radiation Therapy

Biological: Anti-PD-(L)1 based immunotherapy

Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy

Other Names:

Standard of Care

Drug: Platinum based chemotherapy

Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy

Other Names:

Standard of Care

Active Comparator: Control Arm

Participants randomized to the control arm will be treated according to the standard of care.

Biological: Anti-PD-(L)1 based immunotherapy

Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy

Other Names:

Standard of Care

Drug: Platinum based chemotherapy

Standard of care treatment (anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy

Other Names:

Standard of Care

Outcome Measures

Primary Outcome Measures

Median progression-free survival [up to 4 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
3 metastases with at least one measurable extra-hepatic lesion based on modified RECIST (can be primary lesion).
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (All Protocol Activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (All protocol activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (All protocol activities)	Rockville Centre	New York	United States	11553