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

Who is this study for? Patients with renal cell cancer that has spread to the bone
Status: Recruiting
Location: See all (47) locations...
Intervention Type: Procedure, Drug, Other, Radiation
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

⁃ 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

Locations
United States
Alabama
University of Alabama at Birmingham Cancer Center
RECRUITING
Birmingham
California
UC San Diego Moores Cancer Center
RECRUITING
La Jolla
University of California Davis Comprehensive Cancer Center
SUSPENDED
Sacramento
Iowa
UI Health Care Mission Cancer and Blood - Ankeny Clinic
RECRUITING
Ankeny
Iowa Methodist Medical Center
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic
RECRUITING
Des Moines
University of Iowa/Holden Comprehensive Cancer Center
ACTIVE_NOT_RECRUITING
Iowa City
Illinois
Rush MD Anderson Cancer Center
RECRUITING
Chicago
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
Cancer Care Specialists of Illinois - Decatur
RECRUITING
Decatur
Loyola University Medical Center
SUSPENDED
Maywood
UC Comprehensive Cancer Center at Silver Cross
RECRUITING
New Lenox
Rush MD Anderson Cancer Center at Rush Oak Park
RECRUITING
Oak Park
University of Chicago Medicine-Orland Park
RECRUITING
Orland Park
Kansas
University of Kansas Cancer Center
RECRUITING
Kansas City
University of Kansas Cancer Center-Overland Park
SUSPENDED
Overland Park
University of Kansas Hospital-Westwood Cancer Center
RECRUITING
Westwood
Louisiana
East Jefferson General Hospital
RECRUITING
Metairie
LSU Healthcare Network / Metairie Multi-Specialty Clinic
SUSPENDED
Metairie
Tulane University School of Medicine
RECRUITING
New Orleans
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
UMass Memorial Medical Center - University Campus
RECRUITING
Worcester
Michigan
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
RECRUITING
Ann Arbor
Henry Ford Hospital
ACTIVE_NOT_RECRUITING
Detroit
Trinity Health Saint Mary Mercy Livonia Hospital
RECRUITING
Livonia
Minnesota
Minnesota Oncology - Burnsville
RECRUITING
Burnsville
Minnesota Oncology Hematology PA-Maplewood
RECRUITING
Maplewood
Missouri
Siteman Cancer Center at Saint Peters Hospital
RECRUITING
City Of Saint Peters
Siteman Cancer Center at West County Hospital
RECRUITING
Creve Coeur
University of Kansas Cancer Center - North
RECRUITING
Kansas City
University of Kansas Cancer Center - Lee's Summit
RECRUITING
Lee's Summit
Missouri Baptist Medical Center
RECRUITING
St Louis
Siteman Cancer Center-South County
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
North Carolina
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
Duke University Medical Center
RECRUITING
Durham
New York
NYP/Weill Cornell Medical Center
SUSPENDED
New York
Ohio
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
RECRUITING
Pittsburgh
UPMC-Shadyside Hospital
RECRUITING
Pittsburgh
Texas
UT Southwestern Simmons Cancer Center - RedBird
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Fort Worth
RECRUITING
Fort Worth
UT Southwestern Clinical Center at Richardson/Plano
RECRUITING
Richardson
Utah
Huntsman Cancer Institute/University of Utah
RECRUITING
Salt Lake City
Wisconsin
Medical College of Wisconsin
RECRUITING
Milwaukee
Time Frame
Start Date: 2020-07-29
Estimated Completion Date: 2026-10-01
Participants
Target number of participants: 134
Treatments
Experimental: 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.
Active_comparator: 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.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

Similar Clinical Trials