Metastatic Renal Cell CarcinomaPhase 1NCT02406521
Exploratory Study of Radium-223 and VEGF-Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma and Bone Mets
A Phase 1 study testing Pazopanib, Sorafenib and Radium-223 in people with Metastatic Renal Cell Carcinoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Renal Cell Carcinoma
- What is being tested?
- Pazopanib, Sorafenib and Radium-223
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2015to 31 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
- Female participants of childbearing potential must not be pregnant at screening.
- Sexually active participants (men and women) must agree to use highly effective contraceptive methods during the course of the study and for 6 months after completing treatment with radium-223.
Who cannot join
- 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).
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- 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:
- Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.
- Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intraabdominal abscess within 12 weeks before enrollment. Note: Complete healing of an intra-abdominal abscess must be confirmed before enrollment.
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (such as pulmonary hemorrhage) within 4 weeks of enrollment.
- Other clinically significant disorders such as:
- Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or chronic hepatitis B or C infection.
- Serious non-healing wound or ulcer.
- Malabsorption syndrome.
- Symptomatic hypothyroidism.
- Moderate to severe hepatic impairment (Child-Pugh B or C).
- Requirement for hemodialysis or peritoneal dialysis.
- History of solid organ transplantation.
- Major surgery (such as GI surgery) within 6 weeks of enrollment. However, subjects who have had a nephrectomy may be enrolled 4 weeks after surgery, providing there are no wound-healing complications. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. The following are not considered to be major procedures: Thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures.
- QTcF > 470 msec within 4 weeks of enrollment. If the initial QTcF is found to be > 470 ms, two additional EKGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is ≤ 470 ms, the subject meets eligibility in this regard.
- Pregnant or lactating females.
- Inability to swallow tablets or capsules.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- Diagnosis of another malignancy within 2 years of enrollment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy by the principal investigator
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Phase I Study of Radium-223 and Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma and Bone Metastases
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
Read the detailed description
The FDA (the U.S. Food and Drug Administration) has not approved the combination of sorafenib and radium-223 or the combination of pazopanib and radium-223 as a treatment for any disease. Sorafenib and pazopanib are both approved as single agents for the treatment of metastatic renal cell carcinoma. Additionally, radium-223 is FDA approved for the treatment of advanced prostate cancer and has shown to have effects on prostate cancer.
Currently, there are limited options for patients with metastatic renal cell cancer who also have bone metastases. Bone metastases are related to a higher incidence of skeletal complications, including skeletal pain, fractures, spinal cord compression, and an increase in the amount of calcium in blood. Such skeletal complications could result in radiation or surgery to the bone. Since radium-223 is shown to be effective for patients with metastatic prostate cancer who also have bone metastases, researchers want to explore radium-223 with VEGF-targeting therapies to understand how the drug combinations affect safety, quality of life, incidence of skeletal complications, and the progression of cancer.
- Conditions
- Metastatic Renal Cell Carcinoma
- Being tested
- Pazopanib, Sorafenib, Radium-223
- Keywords
- Metastatic renal cell carcinoma, mRCC
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Also called Votrient
SorafenibDrug
Also called Nexavar®
Radium-223Drug
Also called Radium 223 Dichloride, Xofigo®
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Sorafenib; Drug: Radium-223 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarkers of osteoblast and osteoclast activity
Measured: Baseline, 2 Years
Secondary outcomes (15)
Symptomatic skeletal events (SSEs)
Measured: Baseline, 2 Years
Time to SSE
Measured: Baseline, 2 Years
Quality of life using the FKSI-19
Measured: Baseline, 2 Years
Pain using the Brief Pain Inventory (Short Form)
Measured: Baseline, 2 Years
Analgesic use
Measured: Baseline, 2 Years
Overall response rate by RECIST version 1.1
Measured: 2 Years
Duration of response by RECIST version 1.1
Measured: 2 Years
Overall survival
Measured: 2 Years
Progression-free survival
Measured: 2 Years
Response as determined by PERCIST Criteria
Measured: 2 Years
Response as determined by MDA Bone Response Criteria
Measured: 2 Years
Response within bone biomarker subgroups
Measured: 2 Years
Time to first SSE within bone biomarker subgroups
Measured: 2 Years
PFS within bone biomarker subgroups
Measured: 2 Years
OS within bone biomarker subgroups
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionDec 2017
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Mark Pomerantz, MD, Dana-Farber Cancer Institute
- Investigators
- Mark Pomerantz, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02406521
- Sponsor's protocol ID
- 14-523
- Status last verified
- Mar 2020
- First submitted
- 16 Mar 2015
- Last updated
- 4 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Radium-223 and Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma and Bone Metastases
- ClinicalTrials.gov ID
- NCT02406521
- Acronym / sponsor ID
- 14-523
- Conditions
- Metastatic Renal Cell Carcinoma
- Keywords
- Metastatic renal cell carcinoma, mRCC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Apr 2015
- Primary completion
- Dec 2017 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 2 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
The FDA (the U.S. Food and Drug Administration) has not approved the combination of sorafenib and radium-223 or the combination of pazopanib and radium-223 as a treatment for any disease. Sorafenib and pazopanib are both approved as single agents for the treatment of metastatic renal cell carcinoma. Additionally, radium-223 is FDA approved for the treatment of advanced prostate cancer and has shown to have effects on prostate cancer.
Currently, there are limited options for patients with metastatic renal cell cancer who also have bone metastases. Bone metastases are related to a higher incidence of skeletal complications, including skeletal pain, fractures, spinal cord compression, and an increase in the amount of calcium in blood. Such skeletal complications could result in radiation or surgery to the bone. Since radium-223 is shown to be effective for patients with metastatic prostate cancer who also have bone metastases, researchers want to explore radium-223 with VEGF-targeting therapies to understand how the drug combinations affect safety, quality of life, incidence of skeletal complications, and the progression of cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Pazopanib with Radium-223 | Experimental | Drug: Pazopanib, Drug: Radium-223No prior targeted therapy * Pazopanib oral, daily and at predetermined dosage per cycle * Radium-223 predetermined dosage via IV, per cycle |
| Arm B: Sorafenib with Radium-223 | Experimental | Drug: Sorafenib, Drug: Radium-223At least one line of prior targeted therapy: * Sorafenib at predetermined dosage, mouth twice daily * Radium-223 predetermined dosage via IV, per cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (32 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PazopanibAlso: Votrient | Drug | Arm A: Pazopanib with Radium-223 |
| SorafenibAlso: Nexavar® | Drug | Arm B: Sorafenib with Radium-223 |
| Radium-223Also: Radium 223 Dichloride, Xofigo® | Drug | Arm A: Pazopanib with Radium-223, Arm B: Sorafenib with Radium-223 |
Primary outcome
Biomarkers of osteoblast and osteoclast activity
Time frame: Baseline, 2 Years
15 secondary outcomes
Symptomatic skeletal events (SSEs)
Time frame: Baseline, 2 Years
Time to SSE
Time frame: Baseline, 2 Years
Quality of life using the FKSI-19
Time frame: Baseline, 2 Years
Pain using the Brief Pain Inventory (Short Form)
Time frame: Baseline, 2 Years
Analgesic use
Time frame: Baseline, 2 Years
Overall response rate by RECIST version 1.1
Time frame: 2 Years
Duration of response by RECIST version 1.1
Time frame: 2 Years
Overall survival
Time frame: 2 Years
Progression-free survival
Time frame: 2 Years
Response as determined by PERCIST Criteria
Time frame: 2 Years
Response as determined by MDA Bone Response Criteria
Time frame: 2 Years
Response within bone biomarker subgroups
Time frame: 2 Years
Time to first SSE within bone biomarker subgroups
Time frame: 2 Years
PFS within bone biomarker subgroups
Time frame: 2 Years
OS within bone biomarker subgroups
Time frame: 2 Years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Pomerantz, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pazopanib, Sorafenib and Radium-223 in people with Metastatic Renal Cell Carcinoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarkers of osteoblast and osteoclast activity (time frame: Baseline, 2 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.