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.

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: Carcinoma, Renal Cell
• Intervention / Treatment: Radiation: Stereotactic body radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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	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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• De Wolf K, Rottey S, Vermaelen K, Decaestecker K, Sundahl N, De Lobel L, Goetghebeur E, De Meerleer G, Lumen N, Fonteyne V, De Maeseneer D, Ost P. Combined high dose radiation and pazopanib in metastatic renal cell carcinoma: a phase I dose escalation trial. Radiat Oncol. 2017 Sep 22;12(1):157. doi: 10.1186/s13014-017-0893-x.

Study record dates

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: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: EC/2013/1087