ACTIVE_NOT_RECRUITING

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

Conditions

Advanced Renal Cell Carcinoma Chromophobe Renal Cell Carcinoma Clear Cell Renal Cell Carcinoma Collecting Duct Carcinoma Kidney Medullary Carcinoma Metastatic Malignant Neoplasm in the Bone Papillary Renal Cell Carcinoma Stage IV Renal Cell Cancer AJCC v8 Unclassified Renal Cell Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial studies whether adding radium-223 dichloride to the usual treatment, cabozantinib, improves outcomes in patients with renal cell cancer that has spread to the bone. Radioactive drugs such as radium-223 dichloride may directly target radiation to cancer cells and minimize harm to normal cells. Cabozantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving radium-223 dichloride and cabozantinib may help lessen the pain and symptoms from renal cell cancer that has spread to the bone, compared to cabozantinib alone.

Official Title

A Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Advanced Renal Cell Carcinoma With Bone Metastasis (RadiCal)

Quick Facts

Study Start:2020-07-29

Study Completion:2026-10-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04071223

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes of RCC are eligible including but not limited to clear cell, papillary, chromophobe, translocation, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Enrollment of non-clear cell patients will be limited to 20% of the total sample size (\~ 42 patients). Once this goal is met, accrual of non-clear cell patients will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and rhabdoid differentiation are allowed * 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes of RCC are eligible including but not limited to clear cell, papillary, chromophobe, translocation, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Enrollment of non-clear cell patients will be limited to 20% of the total sample size (\~ 42 patients). Once this goal is met, accrual of non-clear cell patients will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and rhabdoid differentiation are allowed
* 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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Rana R McKay

PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Study Locations (Sites)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233

United States

UC San Diego Moores Cancer Center

La Jolla, California, 92093

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

Rush MD Anderson Cancer Center

Chicago, Illinois, 60612

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526

United States

Loyola University Medical Center

Maywood, Illinois, 60153

United States

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451

United States

Rush MD Anderson Cancer Center at Rush Oak Park

Oak Park, Illinois, 60304

United States

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462

United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, 50023

United States

Iowa Methodist Medical Center

Des Moines, Iowa, 50309

United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, 50309

United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242

United States

University of Kansas Cancer Center

Kansas City, Kansas, 66160

United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210

United States

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205

United States

East Jefferson General Hospital

Metairie, Louisiana, 70006

United States

LSU Healthcare Network / Metairie Multi-Specialty Clinic

Metairie, Louisiana, 70006

United States

Tulane University School of Medicine

New Orleans, Louisiana, 70112

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, 01655

United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, 48106

United States

Henry Ford Hospital

Detroit, Michigan, 48202

United States

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154

United States

Minnesota Oncology - Burnsville

Burnsville, Minnesota, 55337

United States

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109

United States

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376

United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141

United States

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154

United States

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

Siteman Cancer Center-South County

St Louis, Missouri, 63129

United States

Missouri Baptist Medical Center

St Louis, Missouri, 63131

United States

NYP/Weill Cornell Medical Center

New York, New York, 10065

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232

United States

UPMC-Shadyside Hospital

Pittsburgh, Pennsylvania, 15232

United States

UT Southwestern Simmons Cancer Center - RedBird

Dallas, Texas, 75237

United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390

United States

UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas, 76104

United States

UT Southwestern Clinical Center at Richardson/Plano

Richardson, Texas, 75080

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Rana R McKay, PRINCIPAL_INVESTIGATOR, Alliance for Clinical Trials in Oncology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-07-29

Study Completion Date2026-10-01

Study Record Updates

Study Start Date2020-07-29

Study Completion Date2026-10-01

Terms related to this study

Additional Relevant MeSH Terms

Advanced Renal Cell Carcinoma
Chromophobe Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma
Collecting Duct Carcinoma
Kidney Medullary Carcinoma
Metastatic Malignant Neoplasm in the Bone
Papillary Renal Cell Carcinoma
Stage IV Renal Cell Cancer AJCC v8
Unclassified Renal Cell Carcinoma