A Phase I Evaluating Integration of HypofractionatedStudy Renal Ablative Radiotherapy

March 7, 2023 updated by: Belal Ahmad, Lawson Health Research Institute

A Phase I Study Evaluating the Integration of Hypofractionated Renal Ablative Radiotherapy in the Setting of Metastatic Renal Cell Carcinoma

  • evaluate the safety and toxicity profile of renal radio-ablation in the setting of metastatic renal cell carcinoma.
  • to assess renal function post radio-ablation
  • Primary and metastatic tumour response to radio-ablation

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A dose limiting toxicity (DLT) will be defined as any grade 3, 4 or 5 toxicity event that is considered to be definitely, probably or possibility related to the protocol radiation therapy. Patients that cannot complete protocol therapy due to acute radiation side-effects will also be considered to be a DLT. The general (non-exhausive) list of organ based toxicity that could be related to this type of radiation therapy include toxicity to the liver, kidney, bowel, spinal cord, and pancreas. Side-effects that are exclusively due to TKI targeted therapy are not considered to be DLT in this protocol.

Three patients will be recruited for the first cohort of the trial. These patients will have the PTV prescribed a dose of 25 Gray to be given in 5 daily fractions over a period of one week (first treatment to start on a Wednesday or Thursday, with planned treatment on successive business days). All therapy should be delivered within 10 business days including any treatment breaks for acute toxicity. After 3 patients have been seen at the 4 week follow up visit, CTCAE version three will be noted. If precisely 1 patient has a DLT, then an additional 3 patients will be recruited to the same cohort and given the same treatment. If no patient has DLT, then a new cohort of 3 patients will be treated to an increased dose of 30 Gray in 5 fractions. Similar criteria will dictate whether the trial ends, or continues with the next cohort being treated to a dose of 35 Gray in 5 daily fractions. There will be a maximum of 4 cohorts (25Gy, 30Gy, 35Gy, and 40Gy) in this study assuming no early DLT issues, each containing 3 or 6 patients. Allowance for a -1 cohort arm of 20 Gy in 5 fractions is made in this protocol for early DLT issues. The diagram below displays the schema in more detail.

Any patient that does not complete protocol therapy due to toxicity issues or is unavailable for the 4-week toxicity assessment is considered to be non-evaluable. These patients will need to be replaced in terms of study accrual. Patients are not to be given TKI therapy during the 4 week window post-RT in order to allow for proper evaluation of the RT intervention; however, the treating oncologist ultimately can override this if it is in the best medical interest of the patient (e.g. progressive and symptomatic systemic disease)

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • 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

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program of the Laswon Research Health Institue

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:

Eligibility Criteria

  • Patients must have histologically confirmed carcinoma of the kidney
  • Patients must be able to tolerate extended treatment time 30 minutes for MVCT and treatment delivery) for radiation on the tomotherapy unit
  • Patients must have confirmed metastatic disease, nodal or locally advanced disease either by biopsy or imaging
  • Informed consent performed and documented
  • Patients must have one of a) unresectable local disease, b) be medically inoperable, or c) chosen against having a local surgical treatment
  • Age ≥ 18
  • Patients previously received any targeted therapy or immunotherapy for RCC, are also eligible. Patients must be off these agents for a minimum of 2 weeks prior to radiation therapy to be eligible

Exclusion Criteria:

  • Patients without an adequate functioning contralateral kidney as seen on renal perfusion scan (>40% of total renal flow)
  • Patients with poor baseline renal function, represented by a creatinine clearance < 50 mL/minute based on the Cockcroft-Gault approximation method
  • Patients with a creatinine clearance < 50 ml/minute are still eligible if the ipsilateral kidney has <25% of the total renal flow on a renal perfusion scan.

еCCr =140 - (Age) × Mass (in kilograms) × constant Serum creatinine ( in µmol/L) constant = male is 1.23, women is 1.04)

  • Previous abdominal radiotherapy
  • Bilateral RCC
  • Diagnosis of transitional cell carcinoma, squamous cell carcinoma, or a non epithelial cancer of the kidney
  • Diagnosis of any other malignancy in previous 5 years, excluding non-melanoma skin cancer -Known active malignancy other than RCC, excluding non-melanoma skin cancer
  • Estimated (by treating radiation oncologist) life expectancy of less than 8 weeks
  • Pregnant or breast-feeding women
  • Concurrent illness in addition to RCC that would make radiotherapy delivery unduly challenging, including but not limited to, severe congestive heart failure or other cardiorespiratory conditions, severe neuromuscular disorders, ongoing or active infections, and psychiatric illness
  • Medical conditions for which radiation is contraindicated, including but not limited to, scleroderma, systemic lupus erythematosus and ataxia teleangiectasia - Patients with excessive kidney motion on pre-planning 4D-CT scan that would prevent safe delivery of radiotherapy with gated or non-gated techniques
  • Patients taking concurrent medication that can interfere with the safe delivery of radiation (e.g. radiosensitizers)
  • Urology opinion recommends partial nephrectomy as cytoreductive atment --Expected TKI therapy to be initiated during initial 2 weeks completion of radiotherapy.

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: Arm 1
Radiation: Radio-Ablation
Radiation: Radio-Ablation
Level I 20Gy/5 Level II 25Gy/5 Level III 30Gy/5 Level IV 35Gy/5 Level V 40Gy/5

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
evaluate the safety/toxicity profile of renal radio-ablation in the setting of metastatic RCC
Time Frame: After 3 patients have been seen at the 4 week follow up visit,
toxicity will be assessed using CTCAE v3
After 3 patients have been seen at the 4 week follow up visit,

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal Function post renal radio-ablation
Time Frame: 4,8,12 wk and every 6months x 5yr
BUN, Creatinine
4,8,12 wk and every 6months x 5yr

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumour Response
Time Frame: 4,8,12 wk and every 6 months x5yr.
CT abdomen evaluting primary disease using RECIST criteria
4,8,12 wk and every 6 months x5yr.

Collaborators and Investigators

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

Sponsor

Lawson Health Research Institute

Investigators

  • Principal Investigator: Belal Ahmad, MD FRCPC, London Regional Cancer Program of the Lawson Health Research Institute

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

July 1, 2009

Primary Completion (Actual)

August 4, 2020

Study Completion (Actual)

August 4, 2020

Study Registration Dates

First Submitted

July 22, 2014

First Submitted That Met QC Criteria

October 9, 2014

First Posted (Estimate)

October 15, 2014

Study Record Updates

Last Update Posted (Estimate)

March 9, 2023

Last Update Submitted That Met QC Criteria

March 7, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Renal Ablation

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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