MRI-Guided Radiation Therapy for the Treatment of Early-Stage Kidney Cancer, the MRI-MARK Trial

October 23, 2024 updated by: M.D. Anderson Cancer Center

MRI-Guided Stereotactic Body Radiotherapy for the Treatment of Early Stage Kidney Cancer: A Single Arm Phase II Clinical Trial (MRI-MARK)

This phase II trial investigates how well MRI-guided stereotactic body radiation therapy works in treating patients with early-stage kidney cancer. Radiation therapy uses high energy radiation to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. This method of radiation delivery is further refined through the incorporation of a MRI into the radiation machine to create a device known as a MRI linear accelerator. During treatment with MRI linear accelerator, continuous MRI images are obtained to allow for real-time treatment monitoring and the ability to adjust treatment plans if minor deviations in anatomy are noted. Giving MRI-guided stereotactic body radiation therapy may help treat patients with early-stage kidney cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate local control following magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy (SBRT) for primary kidney cancer as defined by no growth by imaging at 24 months following SBRT.

SECONDARY OBJECTIVES:

I. To estimate preservation of renal function and to determine frequency of grade 3+ adverse events following SBRT as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

II. To characterize tumor and treated kidney changes by multiparametric MRI, including utility of diffusion and perfusion changes in renal cell carcinoma (RCC) prior to and after SBRT as biomarkers of treatment response.

III. To estimate the rate of pathologic complete response as determined by tumor biopsy at 24 months following SBRT.

IV. To estimate rate of no progression by Response Evaluation Criteria in Solid Tumors (RECIST) at 24 months (less than 20% growth in largest tumor dimension as measured by imaging).

V. To estimate the rates of overall survival and distant metastasis. VI. To evaluate economic strain following SBRT for primary kidney cancer. VII. Compare planned total doses to true total doses delivered to the target and adjacent normal structures, to correlate true delivered doses to normal structures to grade 3+ toxicity, and to determine the rate of cases in which the prescribed isodose line failed to cover 100% of the internal gross tumor volume (iGTV).

OUTLINE:

Patients undergo an MRI scan to check the status and location of the disease, including the motion of the tumor during breathing. Two weeks after MRI, patients undergo SBRT over 1-2 hours on 3 non-consecutive weekdays in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months, then every 6 months thereafter until the end of the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients may enter the study if they are diagnosed with bilateral kidney cancer, multiple lesions in the same kidney, recurrent kidney cancer, or if they have previous or current history of a separate cancer, given all other inclusion criteria met
  • Have a pathologically confirmed diagnosis of renal cell carcinoma (RCC) of any histology
  • Be a suboptimal surgical or ablation candidate, as determined by patient's primary urologist at MD Anderson Cancer Center and by multi-disciplinary consensus. At or before the time of enrollment, a note documenting multidisciplinary consensus supporting active treatment will be recorded in the patient's chart
  • Tumor stage of T1-T2a (i.e. 10cm or less in greatest dimension)
  • Be technically and anatomically appropriate for MRI-guided SBRT, as determined by patient's primary radiation oncologist. Factors considered will include distance between tumor and bowel, tumor movement with respiration as assessed by 4-dimensional (4D) computed tomography (CT) scan, and prior radiotherapy
  • Multi-disciplinary consensus that active treatment is warranted
  • Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Have life expectancy of 2 years or more

Exclusion Criteria:

  • An MRI contraindication (i.e. pacemaker, severe claustrophobia, or MRI-incompatible device)
  • A pre-treatment estimated glomerular filtration rate < 30 cc/min
  • Visceral, nodal, or bony metastatic disease

  • Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit

    • Female subject of childbearing potential should have a negative urine or serum pregnancy within 6 weeks prior to study registration up to the first fraction of radiation
    • Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (MRI-guided SBRT)
Patients undergo an MRI scan to check the status and location of the disease, including the motion of the tumor during breathing. Two weeks after MRI, patients undergo SBRT over 1-2 hours on 3 non-consecutive weekdays in the absence of disease progression or unacceptable toxicity.
Other: Questionnaire Administration
Ancillary studies
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SBRT
  • SABR
  • Stereotactic Ablative Body Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to progression
Time Frame: at 24 months
Local control will be defined as no growth (stability or regression) in the largest dimension of the treated tumor by comparison of magnetic resonance imaging (MRI) images at baseline and 24 months following completion of stereotactic body radiation therapy (SBRT). The local control rate will be compared to case-matched data from patients undergoing active surveillance at MD Anderson Cancer Center. In terms of the primary efficacy analysis, the local control will be evaluated along with the 95% confidence interval. For patients who progress earlier than 24 months will be considered as local control failure and will be included in the confidence interval calculation. In addition, we will estimate the probabilities of local control utilizing the Kaplan Meier method with corresponding 95% confidence intervals.
at 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Preservation of renal function
Time Frame: Baseline to 24 months
Patients will undergo split function renal scans to determine glomerular filtration rate (GFR) at baseline, 12 months, and 24 months. Change in GFR will be reported by diving the difference in GFR at baseline and at the respective follow up visit, by baseline GFR. The change of GFR at follow up visits and baseline will be evaluated by paired t-test. Mixed model will be used to explore the change of GFR over time after taking the within-subject correlation.
Baseline to 24 months
Treatment related toxicities
Time Frame: Up to 24 months after completion of SBRT
The frequency of non-laboratory non-fatigue adverse events will be determined, defined as a grade 3+ event following SBRT, attributed to SBRT, and affecting the ipsilateral kidney or an adjacent organ (contralateral kidney, liver, small bowel, large bowel, stomach, spleen, or nerves) as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Up to 24 months after completion of SBRT
Changes in the imaging of primary tumor and treated kidney
Time Frame: Baseline up to 24 months after completion of SBRT
Patients will undergo MRI of the abdomen at regular intervals (i.e. at 6, 12, 18, and 24 months) permitting analysis of changes in functional imaging biomarkers evaluating tumor and renal perfusion and diffusion, which can be correlated to clinical outcome and toxicities. Mixed model will be used to explore the change of tumor characteristics over time after taking the within-subject correlation. Multi b-value diffusion-weighted imaging (DWI) derived diffusion and perfusion changes will be evaluated over the course of therapy to assess their utility as predictors of renal insufficiency following therapy.
Baseline up to 24 months after completion of SBRT
Pathologic response
Time Frame: At 24 months
All tumors will be biopsied at baseline. When safe and feasible, patients will undergo re-biopsy at 24 months following SBRT. Viability and percent necrosis will be determined by hematoxylin and eosin (H&E) staining. Other stains such as ki67 may be included. Taking pathologic evaluation as gold standard for no viable tumor cells following SBRT, will correlate tumor biopsy results with local control by imaging. McNemar test will also be used to evaluate the agreement between local control (yes versus [vs] no) and pathologic evaluation (responder vs none). Will also calculate sensitivity and specificity of our primary endpoint of local control (no growth by computed tomography [CT] scan at 24 months).
At 24 months
Progression free survival
Time Frame: At 24 months
Will estimate no progression Response Evaluation Criteria in Solid Tumors (RECIST) at 24 months (less than 20% growth in largest tumor dimension) along with the 95% confidence interval (CI).
At 24 months
Distant metastasis-free survival
Time Frame: Up to 24 months
Will estimate the probabilities of patients remaining free from distant metastases utilizing the Kaplan Meier method with corresponding 95% CIs. The log rank test will be used to compare the survival difference between important subgroups (such as tumor categories, etc.). Cox model will be conducted to examine the clinical factor effect on time-to-event variables.
Up to 24 months
Overall survival
Time Frame: Up to 24 months
Will estimate the probabilities of patient survival utilizing the Kaplan Meier method with corresponding 95% CIs. The log rank test will be used to compare the survival difference between important subgroups (such as tumor categories, etc.). Cox model will be conducted to examine the clinical factor effect on time-to-event variables.
Up to 24 months
Economic strain of MRI-guided SBRT
Time Frame: Baseline to 24 months
Assessed using the validated ENRICH questionnaire. Questionnaire scores will be calculated based on standardized manual associated with the instrument. Incomplete surveys (in the event that a participant declines to answer one or more questions) will still be considered valid and will be used for study purposes. Descriptive statistics will be used to summarize scores of the questionnaire. The distribution of each continuous variable will be summarized by its mean, standard deviation, median, and range. The distribution of each categorical variable will be summarized in terms of its frequencies and percentages. We will compare results at each time point to estimate financial toxicity of treatment. The association between patient clinical factor (such as T-stage or histology result) and clinical measurement (e.g., local control, pathologic response, tumor characteristics by MRI) will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Baseline to 24 months
Planned doses
Time Frame: up to 1 month
Will compare planned doses to true total doses delivered to the target and adjacent normal structures.
up to 1 month
Correlation of normal tissue true delivered doses with grade 3+ toxicity
Time Frame: Up to 24 months after completion of SBRT
Will generate target structure and normal tissue dose volume histograms (DVHs) based on the simulation imaging as per routine treatment planning. Verification MR images will then be obtained immediately prior to each delivered fraction, which may or may not prompt an adaptive plan change. Will use the verification MR images and the delivered plan to generate additional target structure and normal tissue DVHs that will approximate "true" delivered dose. Will generate a cumulative true DVH based on each individual fraction, and compare this to the original planning DVH. Normal tissue toxicity will be assessed in light of both the planned and the true DVH. To assess the impact of intrafraction target and normal structure movement, MR images may also be obtained at specified time intervals during an individual treatment fraction.
Up to 24 months after completion of SBRT
Rate of cases in which the prescribed isodose line failed to cover 100% of the internal gross tumor volume (iGTV)
Time Frame: Up to 24 months after completion of SBRT
The frequency of non-laboratory non-fatigue adverse events will be determined per CTCAE version 5.0. These events will be correlated to the true delivered dose received by the associated organ(s). The number of cases in which the prescribed isodose line failed to cover the entirety of the iGTV will be determined, and correlated to outcomes.
Up to 24 months after completion of SBRT

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
M.D. Anderson Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chad Tang, M.D. Anderson Cancer Center

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.

Helpful Links

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 19, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 17, 2021

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 17, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 9, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 23, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020-0168 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2020-06739 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

Clinical Trials on Renal Cell Carcinoma

Clinical Trials on Questionnaire Administration

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings