Exploratory Study of Radium-223 and VEGF-Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma and Bone Mets

NCT02406521 | Completed Phase 1 DMC

• 1 other identifier: 14-523
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is comparing different drug combinations as a possible treatment for metastatic renal cell carcinoma (mRCC) and bone metastases. The names of the study interventions involved in this study are:

• Combination of Radium-223 and Sorafenib
• Combination of Radium-223 and Pazopanib

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Metastatic renal cell carcinoma; mRCC

Outcome Measures

Primary Outcomes (1)

• Biomarkers of osteoblast and osteoclast activity

  Baseline, 2 Years

Secondary Outcomes (15)

• Symptomatic skeletal events (SSEs)

  Baseline, 2 Years

• Time to SSE

  Baseline, 2 Years

• Quality of life using the FKSI-19

  Baseline, 2 Years

• Pain using the Brief Pain Inventory (Short Form)

  Baseline, 2 Years

• Analgesic use

  Baseline, 2 Years

Study Arms (2)

Arm A: Pazopanib with Radium-223

EXPERIMENTAL

No prior targeted therapy * Pazopanib oral, daily and at predetermined dosage per cycle * Radium-223 predetermined dosage via IV, per cycle

Drug: Pazopanib; Drug: Radium-223

Arm B: Sorafenib with Radium-223

EXPERIMENTAL

At least one line of prior targeted therapy: * Sorafenib at predetermined dosage, mouth twice daily * Radium-223 predetermined dosage via IV, per cycle

Drug: Sorafenib; Drug: Radium-223

Interventions

Pazopanib DRUG

Also known as: Votrient

Arm A: Pazopanib with Radium-223

Sorafenib DRUG

Also known as: Nexavar®

Arm B: Sorafenib with Radium-223

Radium-223 DRUG

Also known as: Radium 223 Dichloride, Xofigo®

Arm A: Pazopanib with Radium-223; Arm B: Sorafenib with Radium-223

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Documented pathologic diagnosis of RCC. All subtypes eligible including but not limited to clear cell, papillary, chromophobe, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Sarcomatoid and rhabdoid differentiation are allowed.
• Presence of at least one metastatic bone lesion(s). Patients with non-measurable bone-only disease are allowed.
• ECOG performance status of 0-2 (Appendix A).
• Must have adequate organ and bone marrow function.
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (without use of G-CSF 4 weeks prior to enrollment).
• Platelet count ≥100,000/mm3.
• Hemoglobin ≥ 9 g/dL (transfusions allowed).
• ALT and AST ≤ 3.0 x the upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 x ULN. For participants with Gilbert's disease ≤ 3.0 mg/dL.
• Calculated creatinine clearance ≥ 30 mL/min using the Cockroft-gault equation.
• Urine protein-to-creatinine (UPC) ratio ≤ 2 mg/mg creatinine or 24-hour urine protein \< 2 g.
• Recovery to baseline or ≤ grade 1 CTCAE version 4.0 from toxicities related to any prior treatment, unless adverse events are clinically non-significant and/or stable on supportive therapy.
• Capable of understanding and complying with the protocol requirements and has signed the informed consent document.
• Sexually active participants and their partners must agree to use medically accepted methods of contraception.

You may not qualify if:

• For patients in the sorafenib cohort, no prior therapy with sorafenib is allowed and at least 1 line of prior therapy is required including prior: VEGF-targeting therapy (such as sunitinib, axitinib, tivozanib, bevacizumab), mTOR-targeting therapy (such as everolimus, temsirolimus), immunotherapy (such as anti-PD-1 or anti-PD-L1), cytokine therapy (such as interleukin-2, IFN-a) or cytotoxic systemic chemotherapy allowed.
• For patients in the pazopanib cohort, no prior systemic therapy for mRCC is allowed, with the exception of prior cytokine therapy (such as interleukin-2, IFN-a), immunotherapy (such as anti-PD-1 or anti-PD-L1), or supportive therapies (such as zoledronic acid, denosumab).
• Receipt of any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of enrollment.
• Radiation therapy for bone metastases within 2 weeks, other external radiation therapy within 4 weeks of enrollment.
• Received prior hemibody external radiotherapy.
• Prior therapy with radium-223 or systemic radiotherapy (such as samarium, strontium).
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks of enrollment as documented by MRI or CT imaging. Treated brain metastases are defined as having no ongoing requirement for steroids (must be off steroids for at least 4 weeks) and no evidence of progression or hemorrhage after treatment for at least 4 weeks of enrollment as documented by MRI or CT imaging.
• Imminent or established spinal cord compression based on clinical 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 4 weeks before enrollment.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias.
• uncontrolled hypertension defined as sustained BP \> 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 12 weeks of enrollment.
• Thromboembolic event (such as deep venous thrombosis, pulmonary embolism) within 4 weeks of enrollment.
• GI disorders including those associated with a high risk of perforation or fistula formation:

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bayer: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pazopanib; Sorafenib; Radium-223; radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mark Pomerantz, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: March 16, 2015
• First Posted: April 2, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 31, 2019
• Last Updated: March 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)