Focused Radiation Versus Systemic Therapy for Kidney Cancer Patients With Limited Metastasis, SOAR Study
- Conditions
- Stage IV Renal Cell Cancer AJCC v8Metastatic Renal Cell Carcinoma
- Interventions
- Procedure: Computed TomographyProcedure: Magnetic Resonance ImagingOther: Questionnaire AdministrationProcedure: Stereotactic Ablative RadiotherapyProcedure: Systemic Therapy
- Registration Number
- NCT05863351
- Lead Sponsor
- ECOG-ACRIN Cancer Research Group
- Brief Summary
This phase III trial compares the effect of stero-ablative radiotherapy (SAbR) followed by standard of care systemic therapy, to standard of care systemic therapy alone, in patients with kidney cancer that has spread from where it first started (primary site) to a limited (2-5) number of places in the body (metastatic). Study doctors want to find out if this approach is better or worse than the usual approach for metastatic kidney cancer. The usual approach is defined as the care most people get for metastatic kidney cancer which includes systemic therapy such as immunotherapy (given through the veins) and/or small molecular inhibitor (tablets taken by mouth). Radiotherapy uses high energy x-rays to kill cancer cells and shrink tumors. SAbR uses special equipment to position a patient and deliver radiation to tumors with high precision. Giving SAbR prior to systemic therapy may kill more tumor cells than the usual approach, which is systemic therapy alone.
- Detailed Description
PRIMARY OBJECTIVES:
I. To compare overall survival (OS) between patients receiving SAbR + systemic therapy (SABR+ST) versus systemic therapy (ST) only.
II. To compare average adverse event (AE) score between SAbR+ST arm and ST only arm.
SECONDARY OBJECTIVES:
I. To compare global health status / quality of life (QOL) between patients receiving SAbR+ST versus ST only.
II. To compare progression-free survival (PFS) between the arms.
EXPLORATORY OBJECTIVES:
I. To estimate PFS on first line systemic therapy (PFS-SST) in the SAbR+ST arm and compare with first line systemic therapy PFS of the ST arm.
II. To explore local control from SAbR by looking at the amount of local failures after SAbR in the SAbR+ST arm.
III. To assess the cost-effectiveness between the arms in terms of cost per unit gain in quality-of-life years.
QOL OBJECTIVES:
I. To compare global health status / quality of life (QOL) between patients receiving SabR+ST versus ST only using the National Comprehensive Cancer Network (NCCN) / Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index -19 item (NFKSI-19).
II. To compare quality-adjusted survival between patients randomized to receive SabR+ST vs ST alone using European Quality of Life (EUROQOL) 5-dimension, 5-level (EQ-5D-5L) at 3, 6, 9, 12, 18, and 24 months.
III. To compare global health status / QOL of the NFKSI-19 at all of the 3, 6, 9, 12, 18, and 24 month time points between patients randomized to receive SabR+ST versus ST alone.
IV. To compare scale scores of the NFKSI-19 (disease-related symptoms - physical disease-related symptoms - emotional, treatment side effects, and function \& well-being) at 3, 6, 9, 12, 18, 24 months between patients randomized to receive SabR+ST versus ST alone.
V. To compare time to global quality of life deterioration between patients randomized to receive SabR+ST versus ST alone using NFKSI-19.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive standard of care systemic therapy on study.
ARM II: Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study.
Patients in both arms undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 472
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Patient must be >= 18 years of age
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Patient must have a pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma (RCC) prior to randomization
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Patient may have any RCC histology except a histology that has a sarcomatoid component
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Patient must have primary site addressed by local therapy. If the primary RCC is intact, the patient must undergo local treatment to the primary before randomization
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Patient must have favorable or intermediate International Metastatic RCC Database Consortium (IMDC) risk (0-2) at the time of randomization
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Patient must have a total of between 2 and 5 metastatic lesions, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with imaging obtained within 45 days prior to randomization
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Patient must have a documentation from a radiation oncologist confirming that all sites are amenable to SAbR
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Patient may have received prior therapy in the adjuvant setting as long as potential trial participants have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
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Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
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Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
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All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
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A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
- Has achieved menarche at some point
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
-
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Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
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Patient must have a Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
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Patients must have adequate organ and bone marrow function as per the recommended guidelines and the respective Food and Drug Administration [FDA] package insert required for the systemic therapy chosen by the treating oncologist. We recognize that patients may have varying levels of renal and liver function that will impact which systemic therapy is appropriate for the patient. We do not require all patients to have specific baseline laboratory thresholds but do ask the treating oncologist to attest that the patient has adequate organ and bone marrow function to safely receive one of the first line systemic therapies listed in the protocol as a standard of care treatment option
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study
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For patients with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If no previous history, testing for HBV is not required for entry onto the study
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Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. If no previous history, testing for HCV is not required for entry onto the study
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In order to participate in the QOL portion of the protocol, the patient must speak one of the languages in which the NFKSI-19 and EQ-5D-5L is available
- NOTE: Sites cannot translate the associated QOL forms
- Patient must not have brain metastases
- Patient must not have metastasis involving the following locations: ultra-central (within 2cm of carina) lung, invading gastrointestinal tract (such as esophagus, stomach, intestines, colon, rectum), skin, and scalp
- Patient must not have received any prior systemic therapy (except for adjuvant setting) for metastatic RCC
- Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
- Active tuberculosis (purified protein derivative [PPD] response without active TB is allowed)
- Uncontrolled hypertension (systolic blood pressure [BP] > 190mmHg or diastolic BP > 110mmHg)
- Major surgery within 30 days prior to randomization
- Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 30 days prior to randomization
- Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], cerebrovascular accident [CVA], etc.) events within 180 days prior to randomization
- Moderate or severe hepatic impairment (child-Pugh B or C)
- Untreated pulmonary embolism (PE) or deep-vein thrombosis (DVT) is not allowed. Treated PE or DVT is allowed > 30 days from diagnosis and when not resulting in respiratory impairment
- Unstable cardiac arrhythmia within 180 days prior to randomization
- History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to randomization
- History of or active inflammatory bowel disease
- Malabsorption syndrome within 30 days prior to randomization
- Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
- Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II (SAbR, usual care) Magnetic Resonance Imaging Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm II (SAbR, usual care) Questionnaire Administration Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm I (usual care) Computed Tomography Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm I (usual care) Questionnaire Administration Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm II (SAbR, usual care) Computed Tomography Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm II (SAbR, usual care) Stereotactic Ablative Radiotherapy Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm II (SAbR, usual care) Systemic Therapy Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm I (usual care) Magnetic Resonance Imaging Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial. Arm I (usual care) Systemic Therapy Patients receive standard of care systemic therapy on study. Patients undergo CT or MRI throughout the trial.
- Primary Outcome Measures
Name Time Method Overall survival (OS) From randomization to death from any cause, assessed up to 10 years The repeated confidence interval method will be utilized. At each scheduled interim analysis, a one-sided 95% repeated confidence interval of hazard ratio (stereotactic ablative radiotherapy \[SAbR\] + standard therapy \[ST\] / ST) will be computed, using the partial likelihood estimate, to test non-inferiority in OS for SAbR+ST arm.
Incidence of adverse events (AEs) From randomization up to 6 months All patients who receive treatment, regardless of eligibility, will be evaluated for AE/toxicity. AE score will be calculated in 3-month intervals starting from randomization. To calculate the AE score for a 3-month interval, for each patient, the AE sub-score for each Common Terminology Criteria for Adverse Events (CTCAE) categories (there are 26 AE categories listed in CTCAE version 5) will be aggregated based on the highest grade of AE experienced in each CTCAE category.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) From randomization to progression of disease, assessed up to 10 years Patients randomized to SAbR will need to first progress on SAbR, then progress on systemic therapy to be counted as an event for progression. Progression on SAbR is when SAbR (sequential SAbR) is unable to control the disease by meeting one of the two criteria: \> 6 metastases in total requiring SAbR (no matter how many metastases a patient was randomized with), or one or more progressing lesions not amenable to SAbR (\> 5% risk of grade 3 toxicity by American Society for Therapeutic Radiology and Oncology definition). This endpoint will be compared between the two arms using stratified log-rank test, at one-sided 0.025 significance level.
Trial Locations
- Locations (108)
University of Kansas Cancer Center - North
🇺🇸Kansas City, Missouri, United States
University of Kansas Cancer Center - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
University of Kansas Cancer Center at North Kansas City Hospital
🇺🇸North Kansas City, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
Manhattan Eye Ear and Throat Hospital
🇺🇸New York, New York, United States
Highland Hospital
🇺🇸Rochester, New York, United States
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
HSHS Saint Elizabeth's Hospital
🇺🇸O'Fallon, Illinois, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
UCHealth University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Poudre Valley Hospital
🇺🇸Fort Collins, Colorado, United States
Cancer Care and Hematology-Fort Collins
🇺🇸Fort Collins, Colorado, United States
UCHealth Greeley Hospital
🇺🇸Greeley, Colorado, United States
UCHealth Highlands Ranch Hospital
🇺🇸Highlands Ranch, Colorado, United States
Medical Center of the Rockies
🇺🇸Loveland, Colorado, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
OSF Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
Mission Cancer and Blood - Ankeny
🇺🇸Ankeny, Iowa, United States
Mercy Hospital
🇺🇸Cedar Rapids, Iowa, United States
Oncology Associates at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Mission Cancer and Blood - West Des Moines
🇺🇸Clive, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Mission Cancer and Blood - Des Moines
🇺🇸Des Moines, Iowa, United States
Mission Cancer and Blood - Laurel
🇺🇸Des Moines, Iowa, United States
University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Olathe Health Cancer Center
🇺🇸Olathe, Kansas, United States
University of Kansas Cancer Center-Overland Park
🇺🇸Overland Park, Kansas, United States
University of Kansas Hospital-Indian Creek Campus
🇺🇸Overland Park, Kansas, United States
Salina Regional Health Center
🇺🇸Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus
🇺🇸Topeka, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸Westwood, Kansas, United States
The James Graham Brown Cancer Center at University of Louisville
🇺🇸Louisville, Kentucky, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health Medical Center - Brighton
🇺🇸Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
🇺🇸Canton, Michigan, United States
Trinity Health Medical Center - Canton
🇺🇸Canton, Michigan, United States
Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
🇺🇸Chelsea, Michigan, United States
University of Michigan Health - Sparrow Lansing
🇺🇸Lansing, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸Livonia, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
🇺🇸Ypsilanti, Michigan, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
University of Rochester
🇺🇸Rochester, New York, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
ECOG-ACRIN Cancer Research Group
🇺🇸Philadelphia, Pennsylvania, United States
Sanford Cancer Center Oncology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸Sioux Falls, South Dakota, United States
UT Southwestern Simmons Cancer Center - RedBird
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Fort Worth
🇺🇸Fort Worth, Texas, United States
UT Southwestern Clinical Center at Richardson/Plano
🇺🇸Richardson, Texas, United States
VCU Massey Cancer Center at Stony Point
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States