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.

NCT02334709 | Completed Phase 1

• 1 other identifier: EC/2013/1087
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Response rate

  4 years

• Immunomonitoring

  4 years

Study Arms (1)

SBRT + fixed dose Tyrosine Kinase Inhibitor

EXPERIMENTAL

Single arm phase I trial with 3 dose-escalation arms

Radiation: Stereotactic body radiotherapy

Interventions

Stereotactic body radiotherapy 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).

SBRT + fixed dose Tyrosine Kinase Inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 adequate organ function for TKI treatment.

You may not qualify if:

• prior systemic treatment for RCC
• uncontrolled central nervous metastases
• prior radiotherapy interfering with SBRT
• any disorder precluding understanding of trial information.

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Dept. of Radiotherapy, Ghent University Hospital

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 28938918 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Piet Ost, PhD

  Dept. of Radiotherapy, Ghent University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 8, 2015
• Study Start: February 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: January 11, 2017

Record last verified: 2017-01

Locations

BE (1)