Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Study
Purpose
This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread to other places in the body (metastatic). Radiation therapy uses high energy photons 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 of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
Conditions
- Metastatic Renal Cell Carcinoma
- Stage III Renal Cell Cancer AJCC v8
- Stage IV Renal Cell Cancer AJCC v8
- Unresectable Renal Cell Carcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration - Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup: - History/physical examination within 45 days prior to registration - CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration - Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors) - 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 - Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor - Patient not recommended for or refused immediate cytoreductive nephrectomy - Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen - Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging - Age >= 18 - Karnofsky performance status >= 60 within 45 days prior to registration - Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration) - Platelet count >= 50,000/mm^3 (within 45 days prior to registration) - Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration) - Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to registration) - For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate - Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to registration) - Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior to registration) - Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated - Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load - The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal - The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria
- Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment - Patients with untreated or unstable brain metastases or cranial epidural disease - Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator - Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor - Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration) - Severe, active comorbidity defined as follows: - 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 tuberculosis [TB] is allowed) - Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic BP > 110 mmHg) - Major surgery requiring hospital admission ≤ 28 days prior to registration. - Any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration - Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc) events within 180 days prior to registration - Active New York (NY) Heart Association class 3-4 heart failure symptoms - Moderate or severe hepatic impairment (Child-Pugh B or C) - Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis > 30 days prior to registration is allowed) - Unstable cardiac arrhythmia within 180 days prior to registration - History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration - History of or active inflammatory bowel disease - Malabsorption syndrome within 45 days prior to registration - Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =< 45 days prior to registration
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (standard of care immunotherapy) |
Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib PO BID; avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO QD; OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Arm II (SABR, standard of care immunotherapy) |
Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I. |
|
Recruiting Locations
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
Birmingham, Alabama 35233
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
Contact:
Site Public Contact
501-686-8274
Site Public Contact
501-686-8274
UC San Diego Health System - Encinitas
Encinitas, California 92024
Encinitas, California 92024
Contact:
Site Public Contact
760-536-7700
Site Public Contact
760-536-7700
UC San Diego Moores Cancer Center
La Jolla, California 92093
La Jolla, California 92093
UC San Diego Medical Center - Hillcrest
San Diego, California 92103
San Diego, California 92103
Pacific Central Coast Health Center-San Luis Obispo
San Luis Obispo, California 93401
San Luis Obispo, California 93401
Mayo Clinic in Florida
Jacksonville, Florida 32224-9980
Jacksonville, Florida 32224-9980
Contact:
Site Public Contact
855-776-0015
Site Public Contact
855-776-0015
Miami Cancer Institute
Miami, Florida 33176
Miami, Florida 33176
Contact:
Site Public Contact
786-596-2000
Site Public Contact
786-596-2000
Alton Memorial Hospital
Alton, Illinois 62002
Alton, Illinois 62002
Contact:
Site Public Contact
618-463-7323
Site Public Contact
618-463-7323
Centralia Oncology Clinic
Centralia, Illinois 62801
Centralia, Illinois 62801
Northwestern University
Chicago, Illinois 60611
Chicago, Illinois 60611
Carle at The Riverfront
Danville, Illinois 61832
Danville, Illinois 61832
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois 62526
Decatur, Illinois 62526
Decatur Memorial Hospital
Decatur, Illinois 62526
Decatur, Illinois 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois 60115
DeKalb, Illinois 60115
Carle Physician Group-Effingham
Effingham, Illinois 62401
Effingham, Illinois 62401
Crossroads Cancer Center
Effingham, Illinois 62401
Effingham, Illinois 62401
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134
Geneva, Illinois 60134
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois 60045
Lake Forest, Illinois 60045
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
Mattoon, Illinois 61938
Memorial Hospital East
Shiloh, Illinois 62269
Shiloh, Illinois 62269
Southern Illinois University School of Medicine
Springfield, Illinois 62702
Springfield, Illinois 62702
Contact:
Site Public Contact
217-545-7929
Site Public Contact
217-545-7929
Springfield Clinic
Springfield, Illinois 62702
Springfield, Illinois 62702
Contact:
Site Public Contact
800-444-7541
Site Public Contact
800-444-7541
Memorial Medical Center
Springfield, Illinois 62781
Springfield, Illinois 62781
Carle Cancer Center
Urbana, Illinois 61801
Urbana, Illinois 61801
The Carle Foundation Hospital
Urbana, Illinois 61801
Urbana, Illinois 61801
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois 60555
Warrenville, Illinois 60555
Mary Greeley Medical Center
Ames, Iowa 50010
Ames, Iowa 50010
Contact:
Site Public Contact
515-956-4132
Site Public Contact
515-956-4132
McFarland Clinic - Ames
Ames, Iowa 50010
Ames, Iowa 50010
East Jefferson General Hospital
Metairie, Louisiana 70006
Metairie, Louisiana 70006
LSU Healthcare Network / Metairie Multi-Specialty Clinic
Metairie, Louisiana 70006
Metairie, Louisiana 70006
Louisiana State University Health Science Center
New Orleans, Louisiana 70112
New Orleans, Louisiana 70112
University Medical Center New Orleans
New Orleans, Louisiana 70112
New Orleans, Louisiana 70112
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
Baltimore, Maryland 21201
Contact:
Site Public Contact
800-888-8823
Site Public Contact
800-888-8823
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland 21044
Columbia, Maryland 21044
Contact:
Site Public Contact
443-546-1300
Site Public Contact
443-546-1300
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland 21061
Glen Burnie, Maryland 21061
Contact:
Site Public Contact
410-553-8100
Site Public Contact
410-553-8100
Brigham and Women's Hospital
Boston, Massachusetts 02115
Boston, Massachusetts 02115
Contact:
Site Public Contact
617-724-5200
Site Public Contact
617-724-5200
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
Boston, Massachusetts 02215
Contact:
Site Public Contact
877-442-3324
Site Public Contact
877-442-3324
Saint Joseph Mercy Hospital
Ann Arbor, Michigan 48106
Ann Arbor, Michigan 48106
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
Contact:
Site Public Contact
800-865-1125
Site Public Contact
800-865-1125
Saint Joseph Mercy Brighton
Brighton, Michigan 48114
Brighton, Michigan 48114
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan 48114
Brighton, Michigan 48114
Saint Joseph Mercy Canton
Canton, Michigan 48188
Canton, Michigan 48188
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan 48188
Canton, Michigan 48188
Saint Joseph Mercy Chelsea
Chelsea, Michigan 48118
Chelsea, Michigan 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan 48118
Chelsea, Michigan 48118
Beaumont Hospital - Dearborn
Dearborn, Michigan 48124
Dearborn, Michigan 48124
Contact:
Site Public Contact
248-551-7695
Site Public Contact
248-551-7695
Beaumont Hospital - Farmington Hills
Farmington Hills, Michigan 48336
Farmington Hills, Michigan 48336
Contact:
Site Public Contact
248-551-7695
Site Public Contact
248-551-7695
Sparrow Hospital
Lansing, Michigan 48912
Lansing, Michigan 48912
Contact:
Site Public Contact
517-364-9400
Site Public Contact
517-364-9400
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan 48154
Livonia, Michigan 48154
William Beaumont Hospital-Royal Oak
Royal Oak, Michigan 48073
Royal Oak, Michigan 48073
Contact:
Site Public Contact
248-551-7695
Site Public Contact
248-551-7695
William Beaumont Hospital - Troy
Troy, Michigan 48085
Troy, Michigan 48085
Contact:
Site Public Contact
248-551-7695
Site Public Contact
248-551-7695
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan 48197
Ypsilanti, Michigan 48197
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota 56601
Bemidji, Minnesota 56601
Mayo Clinic in Rochester
Rochester, Minnesota 55905
Rochester, Minnesota 55905
Contact:
Site Public Contact
855-776-0015
Site Public Contact
855-776-0015
Saint Francis Medical Center
Cape Girardeau, Missouri 63703
Cape Girardeau, Missouri 63703
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri 65212
Columbia, Missouri 65212
Contact:
Site Public Contact
573-882-7440
Site Public Contact
573-882-7440
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
Creve Coeur, Missouri 63141
Washington University School of Medicine
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
Siteman Cancer Center-South County
Saint Louis, Missouri 63129
Saint Louis, Missouri 63129
Siteman Cancer Center at Christian Hospital
Saint Louis, Missouri 63136
Saint Louis, Missouri 63136
Siteman Cancer Center at Saint Peters Hospital
Saint Peters, Missouri 63376
Saint Peters, Missouri 63376
Cooper Hospital University Medical Center
Camden, New Jersey 08103
Camden, New Jersey 08103
Contact:
Site Public Contact
856-325-6757
Site Public Contact
856-325-6757
Monmouth Medical Center Southern Campus
Lakewood, New Jersey 08701
Lakewood, New Jersey 08701
Monmouth Medical Center
Long Branch, New Jersey 07740
Long Branch, New Jersey 07740
Cooper CyberKnife Center
Mount Laurel, New Jersey 08054
Mount Laurel, New Jersey 08054
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08903
New Brunswick, New Jersey 08903
Contact:
Site Public Contact
732-235-7356
Site Public Contact
732-235-7356
Community Medical Center
Toms River, New Jersey 08755
Toms River, New Jersey 08755
Lovelace Medical Center-Saint Joseph Square
Albuquerque, New Mexico 87102
Albuquerque, New Mexico 87102
Lovelace Radiation Oncology
Albuquerque, New Mexico 87109
Albuquerque, New Mexico 87109
Glens Falls Hospital
Glens Falls, New York 12801
Glens Falls, New York 12801
Contact:
Site Public Contact
518-926-6700
Site Public Contact
518-926-6700
Stony Brook University Medical Center
Stony Brook, New York 11794
Stony Brook, New York 11794
Contact:
Site Public Contact
800-862-2215
Site Public Contact
800-862-2215
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
Chapel Hill, North Carolina 27599
Sanford Bismarck Medical Center
Bismarck, North Dakota 58501
Bismarck, North Dakota 58501
Sanford Broadway Medical Center
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota 58122
Fargo, North Dakota 58122
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio 44011
Avon, Ohio 44011
Contact:
Site Public Contact
800-641-2422
Site Public Contact
800-641-2422
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio 44122
Beachwood, Ohio 44122
Dayton Physicians LLC-Miami Valley South
Centerville, Ohio 45459
Centerville, Ohio 45459
Miami Valley Hospital South
Centerville, Ohio 45459
Centerville, Ohio 45459
Case Western Reserve University
Cleveland, Ohio 44106
Cleveland, Ohio 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
Columbus, Ohio 43210
Dayton Blood and Cancer Center
Dayton, Ohio 45409
Dayton, Ohio 45409
Contact:
Site Public Contact
937-276-8320
Site Public Contact
937-276-8320
Miami Valley Hospital
Dayton, Ohio 45409
Dayton, Ohio 45409
Dayton Physician LLC-Miami Valley Hospital North
Dayton, Ohio 45415
Dayton, Ohio 45415
Miami Valley Hospital North
Dayton, Ohio 45415
Dayton, Ohio 45415
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio 45005-1066
Franklin, Ohio 45005-1066
Dayton Physicians LLC-Atrium
Franklin, Ohio 45005
Franklin, Ohio 45005
Miami Valley Cancer Care and Infusion
Greenville, Ohio 45331
Greenville, Ohio 45331
Contact:
Site Public Contact
937-569-7515
Site Public Contact
937-569-7515
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio 44060
Mentor, Ohio 44060
University Hospitals Parma Medical Center
Parma, Ohio 44129
Parma, Ohio 44129
University Hospitals Portage Medical Center
Ravenna, Ohio 44266
Ravenna, Ohio 44266
Upper Valley Medical Center
Troy, Ohio 45373
Troy, Ohio 45373
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Oklahoma City, Oklahoma 73104
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania 18103
Allentown, Pennsylvania 18103
UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania 15009
Beaver, Pennsylvania 15009
Carlisle Regional Cancer Center
Carlisle, Pennsylvania 17015
Carlisle, Pennsylvania 17015
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania 16505
Erie, Pennsylvania 16505
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania 17109
Harrisburg, Pennsylvania 17109
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
Mechanicsburg, Pennsylvania 17050
Mechanicsburg, Pennsylvania 17050
UPMC Hillman Cancer Center - New Castle
New Castle, Pennsylvania 16105
New Castle, Pennsylvania 16105
UPMC-Magee Womens Hospital
Pittsburgh, Pennsylvania 15213
Pittsburgh, Pennsylvania 15213
Contact:
Site Public Contact
412-647-2811
Site Public Contact
412-647-2811
UPMC-Saint Margaret
Pittsburgh, Pennsylvania 15215
Pittsburgh, Pennsylvania 15215
Contact:
Site Public Contact
412-784-4900
Site Public Contact
412-784-4900
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania 15232
Pittsburgh, Pennsylvania 15232
Contact:
Site Public Contact
412-647-8073
Site Public Contact
412-647-8073
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania 15232
Pittsburgh, Pennsylvania 15232
Contact:
Site Public Contact
412-621-2334
Site Public Contact
412-621-2334
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania 15237
Pittsburgh, Pennsylvania 15237
Contact:
Site Public Contact
412-367-6454
Site Public Contact
412-367-6454
UPMC-Saint Clair Hospital Cancer Center
Pittsburgh, Pennsylvania 15243
Pittsburgh, Pennsylvania 15243
Contact:
Site Public Contact
412-502-3920
Site Public Contact
412-502-3920
Reading Hospital
West Reading, Pennsylvania 19611
West Reading, Pennsylvania 19611
Contact:
Site Public Contact
610-988-9323
Site Public Contact
610-988-9323
Divine Providence Hospital
Williamsport, Pennsylvania 17754
Williamsport, Pennsylvania 17754
UPMC Memorial
York, Pennsylvania 17408
York, Pennsylvania 17408
Contact:
Site Public Contact
717-724-6760
Site Public Contact
717-724-6760
Medical University of South Carolina
Charleston, South Carolina 29425
Charleston, South Carolina 29425
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota 57104
Sioux Falls, South Dakota 57104
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
Sioux Falls, South Dakota 57117-5134
UT Southwestern Simmons Cancer Center - RedBird
Dallas, Texas 75237
Dallas, Texas 75237
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
Dallas, Texas 75390
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas 76104
Fort Worth, Texas 76104
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas 75080
Richardson, Texas 75080
University of Vermont Medical Center
Burlington, Vermont 05401
Burlington, Vermont 05401
University of Vermont and State Agricultural College
Burlington, Vermont 05405
Burlington, Vermont 05405
West Virginia University Charleston Division
Charleston, West Virginia 25304
Charleston, West Virginia 25304
Contact:
Site Public Contact
304-388-9944
Site Public Contact
304-388-9944
Langlade Hospital and Cancer Center
Antigo, Wisconsin 54409
Antigo, Wisconsin 54409
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin 54701
Eau Claire, Wisconsin 54701
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin 53792
Madison, Wisconsin 53792
Contact:
Site Public Contact
800-622-8922
Site Public Contact
800-622-8922
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin 54449
Marshfield, Wisconsin 54449
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin 53051
Menomonee Falls, Wisconsin 53051
Contact:
Site Public Contact
262-257-5100
Site Public Contact
262-257-5100
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
Contact:
Site Public Contact
414-805-3666
Site Public Contact
414-805-3666
Marshfield Clinic-Minocqua Center
Minocqua, Wisconsin 54548
Minocqua, Wisconsin 54548
ProHealth D N Greenwald Center
Mukwonago, Wisconsin 53149
Mukwonago, Wisconsin 53149
Drexel Town Square Health Center
Oak Creek, Wisconsin 53154
Oak Creek, Wisconsin 53154
Contact:
Site Public Contact
414-805-0505
Site Public Contact
414-805-0505
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin 53066
Oconomowoc, Wisconsin 53066
Contact:
Site Public Contact
262-928-7878
Site Public Contact
262-928-7878
Ascension Saint Mary's Hospital
Rhinelander, Wisconsin 54501
Rhinelander, Wisconsin 54501
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin 54868
Rice Lake, Wisconsin 54868
Ascension Saint Michael's Hospital
Stevens Point, Wisconsin 54481
Stevens Point, Wisconsin 54481
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin 54482
Stevens Point, Wisconsin 54482
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin 53188
Waukesha, Wisconsin 53188
Aspirus Regional Cancer Center
Wausau, Wisconsin 54401
Wausau, Wisconsin 54401
Contact:
Site Public Contact
877-405-6866
Site Public Contact
877-405-6866
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin 53095
West Bend, Wisconsin 53095
Contact:
Site Public Contact
414-805-0505
Site Public Contact
414-805-0505
Marshfield Medical Center - Weston
Weston, Wisconsin 54476
Weston, Wisconsin 54476
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin 54494
Wisconsin Rapids, Wisconsin 54494
Contact:
Site Public Contact
715-422-7718
Site Public Contact
715-422-7718
More Details
- NCT ID
- NCT05327686
- Status
- Recruiting
- Sponsor
- NRG Oncology
Detailed Description
PRIMARY OBJECTIVE: I. To determine whether the addition of stereotactic ablative radiotherapy (SABR) to the primary tumor in combination with immunotherapy improves outcomes compared to immunotherapy alone in patients with metastatic, unresected, renal cell carcinoma (RCC). The primary endpoint is nephrectomy and radiographic progression-free survival (nrPFS) with progression determined as per iRECIST criteria. SECONDARY OBJECTIVES: I. To assess the safety, toxicity and tolerability of the two treatment strategies as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5 in each treatment arm. II. To assess the objective response rate (ORR) by Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) in each treatment arm. III. Nephrectomy and radiographic progression-free survival excluding nephrectomies that were performed for non-protocol specified indications (nephrectomy and radiographic progression-free survival [nrPFS]2). IV. Radiographic progression-free survival (rPFS). V. To assess overall survival (OS) in each treatment arm. VI. To assess the time to subsequent second-line therapy or death in each treatment arm. VII. To assess the rate of cytoreductive nephrectomy in each treatment arm. VIII. To assess treatment-free survival in patients who discontinue therapy for reason other than radiographic disease progression. IX. To assess the ORR by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and iRECIST in the primary renal mass. EXPLORATORY OBJECTIVES: I. To assess composite nrPFS in the predefined histological subgroups below: Ia. Clear cell versus non-clear cell histology. Ib. International Metastatic RCC database consortium (IMDC) intermediate versus poor risk group. Ic. Systemic treatment with immunotherapy-immunotherapy combination versus immunotherapy-vascular endothelial growth factor (VEGF) targeted therapy combination. Id. Sarcomatoid versus non sarcomatoid variant. II. To identify prognostic and predictive biomarkers of response to SABR in the context of immunotherapy based treatment via assessment of tissue and blood based biomarkers. III. To evaluate the abscopal effect of SABR with systemic therapy. IIIa. Compare ORR in non-irradiated target lesions in the control arm patients undergoing immunotherapy alone to the experimental arm undergoing SABR + immunotherapy. IV. To evaluate the impact of treatment on level of inferior vena cava (IVC) thrombus. V. To compare accruing center identified iRECIST progression and centrally identified iRECIST progression events on computed tomography (CT). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive one of the following immunotherapy regimens per physician discretion: nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes every 3 weeks for 4 doses followed by nivolumab IV over 30 minutes every 2 or 4 weeks; pembrolizumab IV over 30 minutes every 3 or 6 weeks and axitinib orally (PO) twice daily (BID); avelumab IV over 60 minutes every 2 weeks and axitinib PO BID; nivolumab IV over 30 minutes every 2 or 4 weeks and cabozantinib PO once daily (QD); OR pembrolizumab IV over 30 minutes every 3 or 6 weeks and lenvatinib PO QD. Treatment with immunotherapy continues in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo SABR on 3 different days over 1-3 weeks and receive immunotherapy as in Arm I. After completion of study treatment, patients are followed up every 6 months for 5 years, and then annually for 3 years.