Stereotactic MR-Adaptive Radiation Therapy for Early-stage Renal Cancer

A Phase II Single-Arm Study Evaluating Toxicity, Outcomes, and Dosimetry Using an MR-guided Linear Accelerator for the Treatment of Early Stage Kidney Cancer

The purpose of this study is to investigate the use of an MR-guided linear accelerator to treat early stage renal cancer patients, considered inoperable or in patients declining surgerys. The study will collect efficacy, toxicity, and dosimetry data and assess the degree of improvement provided by this treatment technique. The primary objective is to evaluate whether magnetic resonance imaging (MRI)-guided radiation therapy (MRgRT) for primary renal cancer has an improved toxicity profile relative to conventional computed tomography (CT) based radiation therapy, as measured by the frequency of grade 2+ adverse events following MRgRT as per Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.

Inclusion Criteria:

1. Patients at or over 18 years old.

2. Patients may enter the study if they are diagnosed with bilateral kidney cancer, recurrent kidney cancer, or if they have previous or current history of a another primary cancer, given all other inclusion criteria met.

3. Have a pathologically confirmed diagnosis of renal cell carcinoma (RCC) of any histology, or radiographic diagnosis if biopsy is not clinically indicated, consistent with standard clinical practice where imaging findings provide sufficient diagnostic certainty. In such cases, biopsy may not be required to avoid additional procedural risk; however, inclusion of patients without histologic confirmation may introduce some diagnostic uncertainty, which will be considered in the interpretation of study results.

4. Patients must be deemed a suboptimal surgical or ablation candidate, as determined by the patient's primary urologist at NYU Langone Health and confirmed by multidisciplinary consensus, or may be individuals who decline surgery or ablation following appropriate clinical evaluation and discussion..

   o At or before the time of enrollment, a note documenting multidisciplinary consensus supporting active treatment will be recorded in the patient's chart.

5. Tumor stage of cT1a-b, cN0, M0 (i.e. less than 7 cm in greatest dimension).

6. Be technically and anatomically appropriate for MRI-guided radiation therapy, as determined by patient's primary radiation oncologist.

   o Factors considered will include distance between tumor and bowel, tumor movement with respiration as assessed by 4-dimensional (4D) imaging, and prior radiotherapy in close proximity to treatment which would lead to high dose overlap from the prior radiation fields.

7. Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

8. Have life expectancy of 2 years or more.

Exclusion Criteria:

1. An MRI contraindication (e.g. severe claustrophobia or MRI-incompatible device). In the event of mild claustrophobia, patients will be permitted to take anti-anxiety medication as required for simulation and treatment.
2. A pre-treatment estimated glomerular filtration rate < 30 cc/min.
3. Visceral, nodal, or bony metastatic disease.
4. Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit.
5. Pregnant or breastfeeding individuals, or individuals of childbearing potential who have a positive pregnancy test at screening or prior to radiation treatment initiation.
6. Individuals of childbearing potential who are unwilling to use one highly effective method of contraception and one additional effective method of contraception, or abstain from heterosexual intercourse, during study participation and for 6 months after completion of study therapy.
7. Previous high dose radiation treatment to an overlapping area.
8. Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
9. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
10. Is on systemic therapy that is reasonably expected to modify radiation sensitivity and cannot be stopped for a sufficient washout period to allow for radiation treatment.