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.

NCT ID: NCT02334709

Last Updated: 2017-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2016-08-31

Brief 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.

Conditions

Carcinoma, Renal Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SBRT + fixed dose Tyrosine Kinase Inhibitor

Single arm phase I trial with 3 dose-escalation arms

Group Type: EXPERIMENTAL

Stereotactic body radiotherapy

Intervention Type: RADIATION

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).

Interventions

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).

Intervention Type: RADIATION

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Radiotherapie

Study Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Piet Ost, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Radiotherapy, Ghent University Hospital

Locations

Dept. of Radiotherapy, Ghent University Hospital

Ghent, Oost-Vlaanderen, Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 28938918 (View on PubMed)

Other Identifiers

EC/2013/1087

Identifier Type: -

Identifier Source: org_study_id