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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05327686




Registration number
NCT05327686
Ethics application status
Date submitted
7/04/2022
Date registered
14/04/2022
Date last updated
15/07/2025

Titles & IDs
Public title
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial
Scientific title
Randomized Phase II Stereotactic Ablative Radiation Therapy (SABR) for Metastatic Unresected Renal Cell Carcinoma (RCC) Receiving Immunotherapy (SAMURAI)
Secondary ID [1] 0 0
NCI-2022-02189
Secondary ID [2] 0 0
NRG-GU012
Universal Trial Number (UTN)
Trial acronym
SAMURAI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Renal Cell Carcinoma 0 0
Stage III Renal Cell Cancer AJCC v8 0 0
Stage IV Renal Cell Cancer AJCC v8 0 0
Unresectable Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Avelumab
Treatment: Drugs - Axitinib
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Bone Scan
Treatment: Drugs - Cabozantinib
Treatment: Surgery - Computed Tomography
Treatment: Other - Ipilimumab
Treatment: Drugs - Lenvatinib
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Other - Nivolumab
Treatment: Other - Pembrolizumab
Treatment: Other - Stereotactic Ablative Radiotherapy

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. Patients also undergo CT scan or MRI throughout the trial. Patients may also undergo a bone scan as clinically indicated and blood sample collection throughout the trial.

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. Patients also undergo CT scan or MRI throughout the trial. Patients may also undergo a bone scan as clinically indicated and blood sample collection throughout the trial.


Treatment: Other: Avelumab
Given IV

Treatment: Drugs: Axitinib
Given PO

Treatment: Surgery: Biospecimen Collection
Undergo collection of blood

Treatment: Surgery: Bone Scan
Undergo bone scan

Treatment: Drugs: Cabozantinib
Given PO

Treatment: Surgery: Computed Tomography
Undergo CT

Treatment: Other: Ipilimumab
Given IV

Treatment: Drugs: Lenvatinib
Given PO

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Other: Nivolumab
Given IV

Treatment: Other: Pembrolizumab
Given IV

Treatment: Other: Stereotactic Ablative Radiotherapy
42 Gy in 3 fractions
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Nephrectomy and radiographic progression-free survival (nrPFS)
Timepoint [1] 0 0
From randomization to last follow-up, up to 8 years
Secondary outcome [1] 0 0
Percentage of participants with complete or partial response
Timepoint [1] 0 0
From randomization to disease progression
Secondary outcome [2] 0 0
Percentage of participants with complete or partial response in the primary renal mass
Timepoint [2] 0 0
From randomization to disease progression
Secondary outcome [3] 0 0
Radiographic progression-free survival (rPFS)
Timepoint [3] 0 0
From randomization to last follow-up, up to 8 years
Secondary outcome [4] 0 0
Nephrectomy and radiographic progression-free survival excluding nephrectomies that were performed for non-protocol specified reasons (nrPFS2)
Timepoint [4] 0 0
From randomization to last follow-up, up to 8 years
Secondary outcome [5] 0 0
Overall survival
Timepoint [5] 0 0
From randomization to last follow-up, up to 8 years
Secondary outcome [6] 0 0
Second-line therapy-free survival
Timepoint [6] 0 0
From randomization to last follow-up, up to 8 years
Secondary outcome [7] 0 0
Percentage of participants who undergo cytoreductive nephrectomy
Timepoint [7] 0 0
From randomization to last follow-up, up to 8 years
Secondary outcome [8] 0 0
Treatment-free survival
Timepoint [8] 0 0
From randomization to last follow-up, up to 8 years
Secondary outcome [9] 0 0
Percentage of participants with grade 3+ and with grade 4+ treatment-related adverse events
Timepoint [9] 0 0
From randomization to last follow-up, up to 8 years

Eligibility
Key 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)

* Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault Equation
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/06/2028
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maine
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
North Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Oklahoma
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
South Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
South Dakota
Country [26] 0 0
United States of America
State/province [26] 0 0
Texas
Country [27] 0 0
United States of America
State/province [27] 0 0
Vermont
Country [28] 0 0
United States of America
State/province [28] 0 0
Virginia
Country [29] 0 0
United States of America
State/province [29] 0 0
Washington
Country [30] 0 0
United States of America
State/province [30] 0 0
West Virginia
Country [31] 0 0
United States of America
State/province [31] 0 0
Wisconsin
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
Ireland
State/province [34] 0 0
Co Dublin

Funding & Sponsors
Primary sponsor type
Other
Name
NRG Oncology
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
William A Hall
Address 0 0
NRG Oncology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05327686