Kidney Cancer Clinical Trial

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, the RadiCaL Study

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.

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Full Description

PRIMARY OBJECTIVE:

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.

After completion of study treatment, patients are followed up every 6 months for up to 5 years from study registration.

View Eligibility Criteria

Eligibility Criteria

Inclusion 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)
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

Study is for people with:

Kidney Cancer

Phase:

Phase 2

Estimated Enrollment:

210

Study ID:

NCT04071223

Recruitment Status:

Recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 42 Locations for this study

See Locations Near You

University of Alabama at Birmingham Cancer Center
Birmingham Alabama, 35233, United States
UC San Diego Moores Cancer Center
La Jolla California, 92093, United States More Info
Site Public Contact
Contact
858-822-5354
[email protected]
Rana R. McKay
Principal Investigator
University of California Davis Comprehensive Cancer Center
Sacramento California, 95817, United States More Info
Site Public Contact
Contact
916-734-3089
Mamta Parikh
Principal Investigator
Rush University Medical Center
Chicago Illinois, 60612, United States More Info
Site Public Contact
Contact
312-942-5498
[email protected]
Thomas C. Westbrook
Principal Investigator
University of Chicago Comprehensive Cancer Center
Chicago Illinois, 60637, United States More Info
Site Public Contact
Contact
773-702-8222
[email protected]
Walter M. Stadler
Principal Investigator
Cancer Care Specialists of Illinois - Decatur
Decatur Illinois, 62526, United States More Info
Site Public Contact
Contact
217-876-4762
[email protected]
Bryan A. Faller
Principal Investigator
Loyola University Medical Center
Maywood Illinois, 60153, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park Illinois, 60462, United States
Mission Cancer and Blood - Ankeny
Ankeny Iowa, 50023, United States More Info
Site Public Contact
Contact
515-282-2921
Joshua Lukenbill
Principal Investigator
Iowa Methodist Medical Center
Des Moines Iowa, 50309, United States More Info
Site Public Contact
Contact
515-241-6727
Joshua Lukenbill
Principal Investigator
Mission Cancer and Blood - Des Moines
Des Moines Iowa, 50309, United States More Info
Site Public Contact
Contact
515-241-3305
Joshua Lukenbill
Principal Investigator
University of Iowa/Holden Comprehensive Cancer Center
Iowa City Iowa, 52242, United States More Info
Site Public Contact
Contact
800-237-1225
Yousef Zakharia
Principal Investigator
University of Kansas Cancer Center
Kansas City Kansas, 66160, United States More Info
Site Public Contact
Contact
913-588-3671
[email protected]
Elizabeth M. Wulff-Burchfield
Principal Investigator
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 More Info
Site Public Contact
Contact
913-588-3671
[email protected]
Elizabeth M. Wulff-Burchfield
Principal Investigator
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 More Info
Site Public Contact
Contact
504-988-1147
[email protected]
Mark Sides
Principal Investigator
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Site Public Contact
Contact
877-442-3324
Bradley A. McGregor
Principal Investigator
UMass Memorial Medical Center - University Campus
Worcester Massachusetts, 01655, United States More Info
Site Public Contact
Contact
508-856-3216
[email protected]
Kriti Mittal
Principal Investigator
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor Michigan, 48106, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Henry Ford Hospital
Detroit Michigan, 48202, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia Michigan, 48154, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Minnesota Oncology Hematology PA-Maplewood
Maplewood Minnesota, 55109, United States More Info
Site Public Contact
Contact
952-993-1517
[email protected]
Daniel M. Anderson
Principal Investigator
Siteman Cancer Center at West County Hospital
Creve Coeur Missouri, 63141, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Hiram A. Gay
Principal Investigator
University of Kansas Cancer Center - North
Kansas City Missouri, 64154, United States More Info
Site Public Contact
Contact
913-588-3671
[email protected]
Elizabeth M. Wulff-Burchfield
Principal Investigator
University of Kansas Cancer Center - Lee's Summit
Lee's Summit Missouri, 64064, United States More Info
Site Public Contact
Contact
913-588-3671
[email protected]
Elizabeth M. Wulff-Burchfield
Principal Investigator
Washington University School of Medicine
Saint Louis Missouri, 63110, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Hiram A. Gay
Principal Investigator
Siteman Cancer Center-South County
Saint Louis Missouri, 63129, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Hiram A. Gay
Principal Investigator
Missouri Baptist Medical Center
Saint Louis Missouri, 63131, United States More Info
Site Public Contact
Contact
314-996-5569
Bryan A. Faller
Principal Investigator
Siteman Cancer Center at Saint Peters Hospital
Saint Peters Missouri, 63376, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Hiram A. Gay
Principal Investigator
NYP/Weill Cornell Medical Center
New York New York, 10065, United States More Info
Site Public Contact
Contact
212-746-1848
Ana M. Molina
Principal Investigator
UNC Lineberger Comprehensive Cancer Center
Chapel Hill North Carolina, 27599, United States More Info
Site Public Contact
Contact
877-668-0683
[email protected]
Tracy L. Rose
Principal Investigator
Duke University Medical Center
Durham North Carolina, 27710, United States More Info
Site Public Contact
Contact
888-275-3853
Michael R. Harrison
Principal Investigator
Ohio State University Comprehensive Cancer Center
Columbus Ohio, 43210, United States More Info
Site Public Contact
Contact
800-293-5066
[email protected]
Yuanquan Yang
Principal Investigator
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States More Info
Site Public Contact
Contact
405-271-8777
[email protected]
Tyler Gunter
Principal Investigator
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh Pennsylvania, 15232, United States More Info
Site Public Contact
Contact
412-647-8073
Ravi Patel
Principal Investigator
UPMC-Shadyside Hospital
Pittsburgh Pennsylvania, 15232, United States More Info
Site Public Contact
Contact
412-621-2334
Ravi Patel
Principal Investigator
UT Southwestern Simmons Cancer Center - RedBird
Dallas Texas, 75237, United States More Info
Site Public Contact
Contact
214-648-7097
[email protected]
Suzanne M. Cole
Principal Investigator
UT Southwestern/Simmons Cancer Center-Dallas
Dallas Texas, 75390, United States More Info
Site Public Contact
Contact
214-648-7097
[email protected]
Suzanne M. Cole
Principal Investigator
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth Texas, 76104, United States More Info
Site Public Contact
Contact
214-648-7097
[email protected]
Suzanne M. Cole
Principal Investigator
UT Southwestern Clinical Center at Richardson/Plano
Richardson Texas, 75080, United States More Info
Site Public Contact
Contact
972-669-7044
[email protected]
Suzanne M. Cole
Principal Investigator
Huntsman Cancer Institute/University of Utah
Salt Lake City Utah, 84112, United States More Info
Site Public Contact
Contact
888-424-2100
[email protected]
Umang Swami
Principal Investigator
Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States More Info
Site Public Contact
Contact
414-805-3666
Deepak Kilari
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Kidney Cancer

Phase:

Phase 2

Estimated Enrollment:

210

Study ID:

NCT04071223

Recruitment Status:

Recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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