Re-Induction After Initial Response With Immune Therapy With Radiotherapy in Lung Cancer

Study Overview
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Brief Summary
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Radiotherapy in combination with different forms of immune therapy improved consistently local tumor control and very interestingly, lead to better systemic tumor control and the induction of specific anti-cancer immunity with a memory effect. In small series, it has been shown that a new long-lasting remission can be induced by irradiating one tumor site in patients who showed cancer progression after an initial response to immune therapy. In these series, the original immune therapy was continued and the treatment was very well tolerated. In this study the progression-free survival after radiotherapy to a single lesion will be investigated in patients with stage IV non-small cell lung cancer (NSCLC), who have at least achieved stable disease with immune therapy alone or concurrent immune therapy and chemotherapy.

Detailed Description
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Radiation has consistently been shown to activate key elements of the immune system. Radiotherapy in combination with different forms of immune therapy such as anti-PD-(L)1, anti-CTLA4,immunocytokines, dendritic cell vaccination and Toll-like receptor agonists improved consistently local tumor control and very interestingly, lead to better systemic tumor control (the abscopal effect) and the induction of specific anti-cancer immunity with a memory effect. Moreover, as PD1/PD-L1 is upregulated by radiation and radiation can overcome resistance for PD-(L)1 blockage, their combination is logical. In small series, it has been shown that a new long-lasting remission can be induced by irradiating one tumor site in patients who showed cancer progression after an initial response to immune therapy. In these series, the original immune therapy was continued and the treatment was very well tolerated. In this study the progression-free survival after radiotherapy to a single lesion will be investigated in patients with stage IV non-small cell lung cancer (NSCLC), who have at least achieved stable disease with immune therapy alone or concurrent immune therapy and chemotherapy.

Official Title
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Re-Induction of a Systemic Immune Response After Initial Response With Immune Therapy With Radiotherapy in Metastatic or Locally Recurrent Lung Cancer

Conditions
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Non-Small Cell Carcinoma of Lung, TNM Stage 4

Intervention / Treatment
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* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IV non-small cell lung cancer Initially a Complete Remission, Partial Remission or Stable Disease under immune therapy alone or concurrent immune therapy and chemotherapy and now progressive disease Able to continue the immune therapy Exclusion Criteria: Not able to continue the already initiated immune therapy Patients with any grade 3 toxocity Patients in whom radiotherapy cannot be delivered, according to the radiation oncologist at the multi-disciplinary patient discussion

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
Intervention Model: Single Group Assignment
Interventional Model Description: Given the objective of this phase II trial and the limited number of patients, no formal statistical analyses are planned. Analysis will be limited to presentation of frequencies and proportions and the report of descriptive statistics (e.g. mean, median and/or range) in tabulated form.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiotherapy<br>Patients continue the same immune therapy they already received and get radiotherapy to one lesion. The lesion may or may not be symptomatic. The preferred radiotherapy dose is 24 Gy in 3 fractions (dosage on the 10 Gy isodose is allowed), but other fractionation schedules (e.g. 30 Gy/ 10 fractions, 20 Gy/ 5 fractions, 20-24 Gy / 1 fraction for SRS (stereotactic radiosurgery)) are allowed if these are standard for a certain location or palliative indication in the body. | Radiation: Radiotherapy<br>* Patients continue the same immune therapy they already received and get radiotherapy to one lesion. The lesion may or may not be symptomatic. The preferred radiotherapy dose is 24 Gy in 3 fractions (dosage on the 10 Gy isodose is allowed), but other fractionation schedules (e.g. 30 Gy/ 10 fractions, 20 Gy/ 5 fractions, 20-24 Gy / 1 fraction for SRS (stereotactic radiosurgery)) are allowed if these are standard for a certain location or palliative indication in the body.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression free survival | 3 months after end of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate irradiated lesion | Remission rate (RECIST 1.0) of the irradiated lesion | 3 months after end of radiotherapy | 
| Remission rate non-irradiated lesion(s) | Remission rate (RECIST 1.0) of the non-irradiated lesion(s) | 3 months after end of radiotherapy | 
| Toxicity | Toxicity evaluation CTCAE4.0 | 3 months after end of radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non small cell lung cancer, immune therapy, radiotherapy