Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, RadiCaL Study
NCT ID: NCT04071223
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
134 participants
INTERVENTIONAL
2020-07-29
2026-10-01
Brief Summary
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Detailed Description
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I. To assess the symptomatic skeletal event (SSE)-free survival of metastatic renal cell cancer (mRCC) patients with bone metastases treated with cabozantinib S-malate (cabozantinib) + radium Ra 223 dichloride (radium-223 dichloride) compared to cabozantinib alone.
SECONDARY OBJECTIVES:
I. To investigate the safety, toxicity and tolerability as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in patients treated with cabozantinib + radium-223 dichloride compared to cabozantinib alone.
II. To assess SSE-free survival of each treatment arm in predefined sub-groups. III. To assess progression-free survival (PFS) in each treatment arm. IV. To assess overall survival (OS) in each treatment arm. V. To assess time to first SSE (defined as first use of radiation therapy to relieve skeletal symptoms, new symptomatic pathologic vertebral or non-vertebral bone fractures, spinal cord compression, or symptomatic tumor-related orthopaedic surgical intervention) in each treatment arm.
VI. To assess the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
VII. To assess time to subsequent anti-cancer systemic therapy and type of systemic therapy.
EXPLORATORY QUALITY OF LIFE OBJECTIVES:
I. To compare patient-reported pain as assessed by the Brief Pain Inventory questionnaire (BPI) between patients randomized to cabozantinib versus cabozantinib + radium-223 dichloride at 6 months.
II. To compare patient-reported pain as assessed by the BPI between patients randomized to cabozantinib versus cabozantinib + radium-223 dichloride at other timepoints.
III. To compare overall health-related quality of life as assessed by the Patient-Reported Outcomes Measurement Information Systems (PROMIS) Global Health 10 between patients randomized to cabozantinib versus cabozantinib + radium-223 dichloride.
IV. To compare quality-adjusted survival (overall survival x utility score assessed by European Quality of Life Five Dimension Five Level Scale \[EQ5D-5L\]) between patients randomized to cabozantinib + radium-223 dichloride.
CORRELATIVE OBJECTIVES:
I. To evaluate changes in the following bone turnover markers between arms:
Ia. Marker of bone formation: P1NP, BSAP. Ib. Marker of bone resorption: CTX, NTX. II. To correlate changes in bone turnover markers with SSE-free survival. III. To assess the immunomodulatory properties of cabozantinib with or without radium-223 dichloride at baseline, during treatment, and at progression.
IV. To identify prognostic and predictive genomic biomarkers of response to cabozantinib and radium-223 dichloride via assessment of tissue, circulating tumor cells (CTCs) and circulating tumor deoxyribonucleic acid (DNA) (cfDNA).
V. To assess the association between bone response according to MD Anderson response criteria and SSE-free survival (FS).
VI. To correlate change in level of total alkaline phosphatase and bone-specific alkaline phosphatase to overall response to cabozantinib + radium-223 dichloride compared to cabozantinib alone.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive radium Ra 223 dichloride intravenously (IV) over 1 minute on day 1 of cycles 1-6 and cabozantinib S-malate orally (PO) once daily (QD) on days 1-28 of every cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cabozantinib S-malate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All patients undergo blood and urine sample collection, bone scan, computed tomography (CT), or magnetic resonance imaging (MRI), and may undergo fludeoxyglucose (FDG)-positron emission tomography (PET) or sodium fluoride (NaF)-PET throughout the study.
After completion of study treatment, patients are followed up every 6 months for up to 5 years from study registration.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A (radium Ra 223 dichloride, cabozantinib s-malate)
Patients receive radium Ra 223 dichloride IV over 1 minute on day 1 of cycles 1-6 and cabozantinib S-malate PO QD on days 1-28 of every cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and urine sample collection, bone scan, CT, or MRI, and may undergo FDG-PET or NaF-PET throughout the study.
Biospecimen Collection
Undergo blood and urine sample collection
Bone Scan
Undergo bone scan
Cabozantinib S-malate
Given PO
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo FDG-PET or NaF-PET
Questionnaire Administration
Ancillary studies
Radium Ra 223 Dichloride
Given IV
Arm B (cabozantinib s-malate)
Patients receive cabozantinib S-malate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and urine sample collection, bone scan, CT, or MRI, and may undergo FDG-PET or NaF-PET throughout the study.
Biospecimen Collection
Undergo blood and urine sample collection
Bone Scan
Undergo bone scan
Cabozantinib S-malate
Given PO
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo FDG-PET or NaF-PET
Questionnaire Administration
Ancillary studies
Interventions
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Biospecimen Collection
Undergo blood and urine sample collection
Bone Scan
Undergo bone scan
Cabozantinib S-malate
Given PO
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Positron Emission Tomography
Undergo FDG-PET or NaF-PET
Questionnaire Administration
Ancillary studies
Radium Ra 223 Dichloride
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Presence of at least 1 metastatic bone lesion not treated with prior radiation is required.
* The presence of bone metastases can be detected by computed tomography (CT), magnetic resonance imaging (MRI), Tc-99m bone scan or positron emission tomography (PET) (fludeoxyglucose F-18 \[FDG\] or sodium fluoride \[NaF\]) imaging. Patients with non-measurable bone-only disease are allowed. Patients may have received prior radiation therapy for bone metastases or other external radiation \>= 7 days prior to registration, as long as they still have at least 1 metastatic bone lesion not treated with radiation. Patients with visceral metastases are allowed, as long as they have at least one untreated bone metastases
* No prior treatment with cabozantinib
* No treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) of registration or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of registration
* No prior hemibody external radiotherapy
* No prior therapy with radium-223 dichloride or systemic radiotherapy (such as samarium, strontium)
* No major surgery within 6 weeks of randomization. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Moh's or other topical skin surgery, Lasik eye surgery are not considered major surgery. Patients who have had a nephrectomy may be registered \>= 3 weeks after surgery, providing there are no wound-healing complications. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
* Recovery to baseline or =\< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy
* The use of osteoclast targeted therapy including either bisphosphonates or denosumab is mandated on this study except in patients with contraindications as determined by the treating investigator, including:
* Hypocalcemia
* Hypophosphatemia
* Renal impairment including those with a glomerular filtration rate (GFR) \< 35 mL/min using the Cockcroft-Gault equation or acute renal impairment
* Hypersensitivity to drug formulation
* Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of jaw (ONJ).
* Use of osteoclast targeted therapy or reason against use needs to be recorded in the electronic case report form (eCRF). Additionally, reason for discontinuation of osteoclast targeted therapy need to be appropriately documented in the eCRF
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
* Therefore, for women of childbearing potential only, a negative urine pregnancy test done =\< 28 days prior to registration is required. A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* Age \>= 18 years
* Karnofsky performance status \>= 60%
* No brain metastases or cranial epidural disease unless 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. 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
* No imminent or established spinal cord compression based on clinical symptoms and/or imaging. In patients with untreated imminent or established spinal cord compression, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
* No imminent or impending pathologic fracture based on clinical symptoms and/or imaging. In patients with untreated imminent or impending pathologic fracture, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
* No significant, uncontrolled intercurrent or recent illness, including but not limited to the following conditions:
* Cardiovascular disorders: Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia; uncontrolled hypertension defined as sustained blood pressure \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment; stroke (including transient ischemic attack), myocardial infarction, or other ischemic event, within 6 months before randomization; thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization
* Gastrointestinal disorders: Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 3 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization
* No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization
* No lesions invading major pulmonary blood vessels
* No other clinically significant disorders:
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]) with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]), if indicated
* 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 (with no medications prohibited by this protocol \[e.g. drug-drug interactions\])
* No serious non-healing wound or ulcer
* No malabsorption syndrome
* No uncompensated/symptomatic hypothyroidism
* No moderate to severe hepatic impairment (Child-Pugh B or C)
* No requirements for hemodialysis or peritoneal dialysis
* No history of solid organ transplantation
* No chronic concomitant treatment with strong CYP3A4 inducers or inhibitors. Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
* No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants include:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 9 g/dl (transfusions allowed)
* Calculated (calc.) creatinine clearance \>= 30 mL/min using the Cockcroft-Gault equation
* Total bilirubin =\< 1.5 x upper limit of normal (ULN), for patients with Gilberts disease =\< 3.0 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x ULN
* Urine protein to creatinine (UPC) ratio =\< 2 mg/mg OR 24-hr urine protein \< 2 g
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Rana R McKay
Role: PRINCIPAL_INVESTIGATOR
Alliance for Clinical Trials in Oncology
Locations
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Rush MD Anderson Cancer Center
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States
Rush MD Anderson Cancer Center at Rush Oak Park
Oak Park, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, United States
Iowa Methodist Medical Center
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
East Jefferson General Hospital
Metairie, Louisiana, United States
LSU Healthcare Network / Metairie Multi-Specialty Clinic
Metairie, Louisiana, United States
Tulane University School of Medicine
New Orleans, Louisiana, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, United States
Minnesota Oncology - Burnsville
Burnsville, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
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
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Missouri Baptist Medical Center
St Louis, Missouri, United States
NYP/Weill Cornell Medical Center
New York, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 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
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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Facility Contacts
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References
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Bade RM, Schehr JL, Emamekhoo H, Gibbs BK, Rodems TS, Mannino MC, Desotelle JA, Heninger E, Stahlfeld CN, Sperger JM, Singh A, Wolfe SK, Niles DJ, Arafat W, Steinharter JA, Jason Abel E, Beebe DJ, Wei XX, McKay RR, Choueri TK, Lang JM. Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma. Mol Oncol. 2021 Sep;15(9):2330-2344. doi: 10.1002/1878-0261.12931. Epub 2021 Mar 3.
Other Identifiers
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NCI-2019-05619
Identifier Type: REGISTRY
Identifier Source: secondary_id
A031801
Identifier Type: OTHER
Identifier Source: secondary_id
A031801
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2019-05619
Identifier Type: -
Identifier Source: org_study_id