A Phase II Trial of Stereotactic Body Radiotherapy With Concurrent Anti-PD1 Treatment in Metastatic Melanoma.

Study Overview
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Brief Summary
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We hypothesize that combining anti-PD1 treatment with radiotherapy might result in improved clinical response rates and PFS compared to anti-PD1 treatment in monotherapy. The current phase II trial aims at exploring the suggested benefits of the combination and aims to improve local and distant tumour responses by exploiting the pro-immunogenic effects of radiotherapy in addition to anti-PD1 treatment.

Official Title
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A Phase II Trial of Stereotactic Body Radiotherapy With Concurrent Anti-PD1 Treatment in Metastatic Melanoma.

Conditions
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Melanoma

Intervention / Treatment
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* Radiation: stereotactic body radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations. Histologically confirmed diagnosis of melanoma At least 3 extracranial measurable metastatic lesions per RECIST v1.1. All radiology studies must be performed within 28 days prior to registration First line anti-PD1 treatment. Karnofsky Performance status > 60 Age 18 years or older Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment Female participants who are breastfeeding or plan to breastfeed should be instructed to discontinue nursing during treatment. Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study treatment Demonstrate adequate organ function defined as the following: AST and ALT ≤2.5 X ULN or ≤5 X ULN with liver metastases Serum total bilirubin ≤1.5 X ULN or direct bilirubin ≤ULN for patient with total bilirubin level >1.5 ULN Serum creatinine ≤1.5 X ULN Absolute neutrophil count >1,000 /mcL Platelets >75,000 /mcL Hemoglobin >9 g/dL or > 5.6 mmol/L No history of active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents Prior malignancy: Subjects who have had another malignancy should be disease-free for 5 years, or should have a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma No evidence of interstitial lung disease No uncontrolled central nervous metastases and/or carcinomatous meningitis. No prior radiotherapy interfering with SBRT. No concomitant therapy with IL-2, interferon, other immunotherapy regimens, chemotherapy, immunosuppressive agent or chronic use of systemic corticosteroids. No active infection requiring systemic therapy No known history of human immunodeficiency virus (HIV) No known active Hepatitis B or Hepatitis C Did not receive a live vaccine within 30 days prior to start of study treatment No mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study Patient not unlikely to comply with the protocol; i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-PD1 treatment in combination with SBRT<br>Patients receiving anti-PD1 treatment will be treated with high-dose radiotherapy to one lesion in 3 fractions prior to the second cycle of systemic therapy. | Radiation: stereotactic body radiotherapy<br>* In patients with metastatic melanoma, anti-PD-1 treatment will be combined with stereotactic body radiotherapy (SBRT). A total dose of 24 Gy SBRT will be delivered in 3 fractions to one measurable lesion and fractions will be separated >48h and <96h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Objective responses will be measured using RECIST v1.1. Objective responses will be defined as the number of patients with complete or partial responses as best response during follow-up. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic responses | Immunologic responses will be assessed using peripheral blood samples, analyzed with FACS phenotyping, functional testing and ELISA. Changes in immunological parameters in tissue will be analyzed using immunohistochemistry. | 12 weeks |