Clear Cell Renal Cell Carcinoma Clinical Trial
Official title:
A Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Advanced Renal Cell Carcinoma With Bone Metastasis (RadiCal)
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.
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. All patients undergo blood 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. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03163667 -
CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)
|
Phase 2 | |
Terminated |
NCT02628535 -
Safety Study of MGD009 in B7-H3-expressing Tumors
|
Phase 1 | |
Withdrawn |
NCT02307474 -
A Pilot Study of SBRT With Adjuvant Pazopanib for Renal Cell Cancer
|
N/A | |
Completed |
NCT00101114 -
Sorafenib and Interferon Alfa in Treating Patients With Metastatic or Unresectable Kidney Cancer
|
Phase 2 | |
Completed |
NCT00078858 -
Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
Recruiting |
NCT05363631 -
Seleno-L Methionine (SLM)-Axitinib-Pembrolizumab
|
Phase 1/Phase 2 | |
Terminated |
NCT01198158 -
Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
|
Phase 3 | |
Completed |
NCT00378703 -
Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer
|
Phase 2 | |
Recruiting |
NCT06138496 -
Cadonilimab Combination With Lenvatinib as Neoadjuvant Therapy for ccRCC
|
Phase 2 | |
Recruiting |
NCT06088134 -
Contrast-enhanced CT-based Deep Learning Model for Preoperative Prediction of Disease-free Survival (DFS) in Localized Clear Cell Renal Cell Carcinoma (ccRCC)
|
||
Recruiting |
NCT06049576 -
Nivolumab and Ipilimumab With and Without Camu Camu for the Treatment of Patients With Metastatic Renal Cell Carcinoma
|
Phase 1 | |
Active, not recruiting |
NCT01038778 -
Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT05536141 -
A Phase 1 Study of AB521 Monotherapy and Combination Therapies in Renal Cell Carcinoma and Other Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05119335 -
A Study of NKT2152, a HIF2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma
|
Phase 1/Phase 2 | |
Completed |
NCT01243359 -
Sunitinib Malate and Bevacizumab in Treating Patients With Kidney Cancer or Advanced Solid Malignancies
|
Phase 1 | |
Terminated |
NCT00098618 -
Sorafenib and Interferon Alfa in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
|
Phase 2 | |
Recruiting |
NCT05620134 -
Study of JK08 in Patients With Unresectable Locally Advanced or Metastatic Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT06052852 -
Study of BDC-3042 as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies
|
Phase 1/Phase 2 | |
Completed |
NCT03680521 -
Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma
|
Phase 2 | |
Recruiting |
NCT06195150 -
Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer
|