Phase I/II Trial of Stereotactic Body Radiotherapy With Concurrent Fixed Dose Tyrosine Kinase Inhibitors in Metastatic Renal Cell Carcinoma: Dose Limiting Toxicity and Abscopal Effect.

Study Overview
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Brief Summary
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Tyrosine kinase inhibitors (TKIs) are often used in the standard treatment for patients with metastasized renal cell carcinoma. In addition to their ability to specifically inhibit tumor growth, TKIs also interfere with the vascularisation of the tumor. Unfortunately, most patients do not obtain long-lasting clinical benefit from this treatment. The goal of the current study is to enhance the effect of TKIs by combining them with stereotactic radiotherapy treatment of one of the metastases. This type of radiotherapy allows us to precisely irradiate the tumor with minimal effect on the surrounding healthy tissue. Recently it has been demonstrated that this type of radiotherapy stimulates the immune system to attack the tumor. By combining stereotactic radiotherapy with TKIs we expect to observe a reduction of metastases in a bigger population of patients. In the first part of our study we focus on the safety of the combination therapy. In the second part we will evaluate the combined treatment response.

Official Title
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Phase I/II Trial of Stereotactic Body Radiotherapy With Concurrent Fixed Dose Tyrosine Kinase Inhibitors in Metastatic Renal Cell Carcinoma: Dose Limiting Toxicity and Abscopal Effect.

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Radiation: Stereotactic body radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent diagnosis of RCC with clear-cell component histology at least 3 extracranial measurable metastatic lesions per RECIST Karnofsky Performance score >60 patients should have undergone cytoreductive treatment of their RCC at least 6 weeks prior to inclusion patients should have adequate organ function for TKI treatment. Exclusion Criteria: prior systemic treatment for RCC uncontrolled central nervous metastases prior radiotherapy interfering with SBRT any disorder precluding understanding of trial information.

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: SBRT + fixed dose Tyrosine Kinase Inhibitor<br>Single arm phase I trial with 3 dose-escalation arms | Radiation: Stereotactic body radiotherapy<br>* A first line TKI will be administered according to the standard dosing of the drug for metastatic RCC during a 1-week run-in period after which SBRT will be delivered to the largest metastatic lesion concurrently with the TKI. The SBRT dose will be escalated in 3 dose levels, starting at 24Gy (8 Gy per fraction), followed by 30 Gy (10 Gy per fraction) and 36 Gy (12 Gy per fraction).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity | Dose limiting toxicity will be assessed before start of TKI, before SBRT, at the end of SBRT and at each follow-up visit | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Response rate will be evaluated at 12 weeks following the start of TKI. | 4 years | 
| Immunomonitoring | Immunomonitoring before start of TKI, before SBRT and 2 weeks after SBRT. | 4 years |