Interstitial Brachytherapy for the Treatment of Unresectable/Unablatable Kidney Cancer

Study Overview
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Brief Summary
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This phase I/II trial investigates the side effects of interstitial brachytherapy and to see how well it works in limiting the growth of large kidney cancer masses in patients with kidney cancer that have refused or are unable to undergo surgery or ablation (unresectable/unablatable). Brachytherapy, also known as internal radiation therapy, temporarily introduces a radiation source into or near the tumor to eradicate the tumor cells. Giving brachytherapy may potentially reduce the size of the kidney cancer mass that would otherwise not be amenable to surgical management and translate into lower risk of spread.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the safety and feasibility of renal interstitial radiation therapy (interstitial brachytherapy). (Safety Lead-In) II. To evaluate local control of renal interstitial brachytherapy. (Expansion Phase) SECONDARY OBJECTIVES: I. To evaluate treatment response of the primary tumor. II. To evaluate 12 month distant progression free survival. III. To evaluate the 12 month volumetric growth of the primary tumor mass. IV. To determine biomarkers predicting response and resistance to radiation treatment. OUTLINE: Patients undergo interstitial brachytherapy for 1-2 fractions in the absence of disease progression or unacceptable toxicity. Patients who undergo 2 fractions may receive both fractions in the same day or on 2 separate days over 2 weeks. After completion of study treatment, patients are followed up every 3 months for at least 3 years.

Official Title
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Prospective Study of Interstitial Brachytherapy for Unresectable/Unablatable T1b/T2a Renal Masses

Conditions
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Stage I Renal Cell Cancer, Stage II Renal Cell Cancer

Intervention / Treatment
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* Procedure: Interstitial Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elected to undergo interstitial brachytherapy as part of conventional treatment for renal cell carcinoma Biopsy proven renal cell carcinoma No definitive evidence of locally advanced (nodal or tumor thrombus) or distant (metastatic) disease Lesion size (maximal dimension) of 4 to 10 cm Patient not a candidate for curative surgery (unwilling or unable to pursue surgery) Lesion cannot be reliably treated with ablative techniques Entire lesion able to be treated adequately by brachytherapy per radiation oncologist Tumor predominantly solid (  > 80%) Lesion that has been observed for >= 6 months with demonstrable growth rate anticipated to be >= 4 mm/year by same imaging modality Renal tumor that is amenable to percutaneous access for interstitial renal brachytherapy (Institutional Review Board [IRB]) Hemoglobin > 9 Absolute neutrophil count (ANC) >= 1500/uL (microliter) Platelets >= 100,000/uL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 upper limit of normal (ULN) Total bilirubin =< ULN A competent immune system Estimated glomerular filtration rate (eGFR) >= 30 Good performance status (Eastern Cooperative Oncology Group [ECOG]) < 2 Understanding and willingness to provide consent No prior systemic treatment for kidney cancer Women of childbearing potential must have negative pregnancy test at start of therapy Exclusion Criteria: Presence of an active, untreated, non-renal malignancy Uncontrolled medical illness including infections, hypertension, arrhythmias, heart failure, or myocardial infarction within 6 months History of bleeding diathesis or recent bleeding episode Need for urgent treatment of renal cancer due bleeding, pain, or paraneoplastic syndrome Prior surgery or radiation therapy to the operative site Unwillingness to undergo clinical and laboratory monitoring and/or imaging studies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (interstitial brachytherapy)<br>Patients undergo interstitial brachytherapy for 1-2 fractions in the absence of disease progression or unacceptable toxicity. Patients who undergo 2 fractions may receive both fractions in the same day or on 2 separate days over 2 weeks. | Procedure: Interstitial Radiation Therapy<br>* Undergo interstitial brachytherapy<br>* Other names: Implant Radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | A 3+3 safety lead-in phase will be employed in order to determine the DLT for interstitial renal brachytherapy. Grading of DLTs will follow the guidelines provided in the Common Terminology Criteria for Adverse Events version 5.0 criteria. | From the first administration of study therapy up to 60 days | 
| One year (12-month) linear growth rate | Adequate local control will be defined as minimal growth kinetics (=< 1 mm/year) on 1 year follow-up. | At 1 year |