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.

January 9, 2017 updated by: Radiotherapie, University Hospital, Ghent

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • Oost-Vlaanderen
      • Ghent, Oost-Vlaanderen, Belgium, 9000
        • Dept. of Radiotherapy, Ghent University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SBRT + fixed dose Tyrosine Kinase Inhibitor
Single arm phase I trial with 3 dose-escalation arms
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).

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Ghent

Investigators

  • Principal Investigator: Piet Ost, PhD, Dept. of Radiotherapy, Ghent University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

January 6, 2015

First Submitted That Met QC Criteria

January 6, 2015

First Posted (Estimate)

January 8, 2015

Study Record Updates

Last Update Posted (Estimate)

January 11, 2017

Last Update Submitted That Met QC Criteria

January 9, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EC/2013/1087

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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