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Ablative tReatment of Inoperable REnal Cell Carcinoma Using STereotactic Body Radiotherapy (ARREST-study)

Phase 2
Terminated
Conditions
Renal Cell Carcinoma
Interventions
Radiation: ARREST-study
Registration Number
NCT02853162
Lead Sponsor
UMC Utrecht
Brief Summary

Phase II study (n=30) to evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) with fiducial markers in inoperable patients with renal cell carcinoma (RCC).

Detailed Description

Rationale: The standard treatment of RCC is (partial-) nephrectomy. Alternatives to this treatment are less invasive techniques like radio frequency ablation (RFA) and cryoablation (CA). Stereotactic body radiation therapy (SBRT) is an alternative curative treatment modality, which has shown promising results in several North-American phase I-II studies over the last years. In this study, we aim to evaluate the safety and feasibility of SBRT for patients with inoperable RCC on a conventional cone beam computed tomography (CBCT) linear accelerator.

Objective: To evaluate safety and feasibility of stereotactic body radiation therapy (SBRT) with fiducial markers in inoperable patients with renal cell carcinoma (RCC).

Study design: Single arm prospective study. Study population: Inoperable patients ≥ 18 years, with a pathology proven RCC fulfilling the inclusion criteria.

Intervention: Prior to treatment, patients will undergo fiducial marker placement (in combination with a biopsy, if RCC has not been pathology proven), followed by a contrast enhanced planning computed tomography (CT)-scan and a contrast enhanced MRI-scan. Fiducial markers will be used as this increases visibility of the tumor and therefore the accuracy of radiotherapy, particularly the irradiated healthy kidney tissue will be diminished by using this approach. Baseline toxicity and quality of life will be assessed.

SBRT using a VMAT technique will be delivered in five fractions of 7 Gy every other day. The target volume for treatment is defined on a 4D planningCT and MRI and the tumor is treated in the midposition of the breathing cycle. After treatment, follow-up will be at 1, 3, 6 and 12 months at the Radiotherapy department, followed by standard follow-up by the urologist. An additional contrast enhanced MRI scan will be performed after the 2nd treatment fraction, and after 6 and 12 months to assess treatment response to prepare for future MR-guided (MR-linac) radiotherapy. Toxicity and quality of life will be assessed during follow-up.

Main study parameters/endpoints: Newly developed acute toxicity grade 3 or more according to the Common Terminology Criteria for Adverse Events (CTC-AE) version 4.0.

The treatment is considered successful if all 5 treatments are completed and if in total \<15% of the patients (=5 patients) report a toxicity ≤ grade 3.

Secondary endpoints will be treatment response, (late) toxicity assessment, local control rate and quality of life assessment.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Inoperability, or when a patient refuses surgery (i.e. not eligible for (partial-) nephrectomy or RFA);
  • Kidney function allows for intervention, as evaluated by treating urologist (taking into account eGFR and renogram);
  • Age ≥ 18 years;
  • Written informed consent;
  • Diagnosis of RCC confirmed by pathology (in case determined after informed consent, patients who are not eligible anymore (no RCC) will be excluded).
Exclusion Criteria
  • Evidence of metastatic disease;
  • Exclusion criteria for contrast enhanced MRI scan, according to the protocol of the department of Radiology, UMC Utrecht;
  • Patients with one functioning kidney;
  • Prior renal surgery (partial nephrectomy);
  • Prior radiotherapy on upper abdomen;
  • Unsafe to have fiducial marker implantation: i.e. anticoagulant agents use other than acetylsalicyl acid, which cannot be safely stopped/bridged for implantation:
  • WHO ≥ 3.
  • Chemotherapy < 3 weeks before treatment;
  • Targeted therapy (sunitinib, etc.) ≤ 7 days before treatment.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ARREST-studyARREST-studySBRT renal cell carcinoma 5 times 7Gy
Primary Outcome Measures
NameTimeMethod
Number of participants with treatment related adverse events grade >2 as assessed by CTCAE v.4.0Within 90 days after radiotherapy

The treatment is considered successful if all 5 treatments are completed and if in total \<15% of the patients (=5 patients) report an acute toxicity ≤ grade 3

Secondary Outcome Measures
NameTimeMethod
Overall survival5 years after radiotherapy

Overall survival

Disease specific survival5 years after radiotherapy

Disease specific survival

Radiological response5 years after radiotherapy

Radiological treatment response of the tumor, measured according to the RECIST criteria, in combination with functional imaging parameters (multiparametric MRI).

Number of participants with correlation of functional MRI (DCE and DWI) changes during treatment and radiological response after treatment12 months after radiotherapy

Response prediction (contrast enhanced MRI during treatment, after 2nd fraction)

Acute and late toxicity5 years after radiotherapy

Common Terminology Criteria for Adverse Events (CTC-AE) version 4.0

Quality of life questionnaire12 months after radiotherapy

EORTC-QLQ-C30

Trial Locations

Locations (1)

UMC Utrecht

🇳🇱

Utrecht, Netherlands

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