NRG-GU012: Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Study (SAMURAI)
Primary Objective
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
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.
To assess the objective response rate (ORR) by iRECIST in each treatment arm.
Nephrectomy and radiographic progression-free survival excluding nephrectomies
that were performed for non-protocol specified indications (nrPFS2).
Radiographic progression-free survival (rPFS) .
To assess overall survival (OS) in each treatment arm.
To assess the time to subsequent second-line therapy or death in each treatment arm.
To assess the rate of cytoreductive nephrectomy in each treatment arm.
To assess treatment-free survival in patients who discontinue therapy for reason
other than radiographic disease progression.
To assess the ORR by RECIST version 1.1 and iRECIST in the primary renal mass.
Pembrolizumab (MK-3475)
Axitinib
Opdivo (Nivolumab)
IPILIMUMAB (MDX-010)
Lenvatinib (E7080/MK-7902)
Radiotherapy
- Rutgers Cancer Institute of New Jersey
- RWJBarnabas Health
- Community Medical Center
- Monmouth Medical Center
- Monmouth Medical Center Southern Campus
- Monmouth Medical Center Vantage Point Center
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
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.