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.

Carcinoma, Renal Cell Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02334709
• Other study ID #: EC/2013/1087
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 6, 2015
• Last updated: January 9, 2017
• Start date: February 2014
• Est. completion date: August 2016

Study information

• Verified date: January 2017
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Radiation:
• Stereotactic body radiotherapy
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).

Locations

Country	Name	City	State
Belgium	Dept. of Radiotherapy, Ghent University Hospital	Ghent	Oost-Vlaanderen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Response rate	Response rate will be evaluated at 12 weeks following the start of TKI.	4 years	No
Secondary	Immunomonitoring	Immunomonitoring before start of TKI, before SBRT and 2 weeks after SBRT.	4 years	No