A Phase I Evaluating Integration of HypofractionatedStudy Renal Ablative Radiotherapy

Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02264548
• Other study ID #: Renal Ablation
• Status: Completed
• Phase: Phase 1
• Start date: July 2009
• Est. completion date: August 4, 2020

Study information

• Verified date: March 2023
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

• 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

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: August 4, 2020
• Est. primary completion date: August 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

?CCr =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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

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

Locations

Country	Name	City	State
Canada	London Regional Cancer Program of the Laswon Research Health Institue	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumour Response	CT abdomen evaluting primary disease using RECIST criteria	4,8,12 wk and every 6 months x5yr.
Primary	evaluate the safety/toxicity profile of renal radio-ablation in the setting of metastatic RCC	toxicity will be assessed using CTCAE v3	After 3 patients have been seen at the 4 week follow up visit,
Secondary	Renal Function post renal radio-ablation	BUN, Creatinine	4,8,12 wk and every 6months x 5yr