Hereditary Clear Cell Renal Cell CarcinomaNCT00727532
Sorafenib in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
A study testing Sorafenib in people with Hereditary Clear Cell Renal Cell Carcinoma and Kidney Cancer, run by Northwestern University at 1 site in United States.
Trial summary
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sorafenib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Hereditary Clear Cell Renal Cell Carcinoma, Kidney Cancer
- What is being tested?
- Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Sep 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed clear cell renal cell carcinoma, meeting 1 of the following criteria:
- Localized disease, as evidenced by intact, bulky, and primary renal lesions (T1 > 3 cm, any T2, T3, or T4) appropriate for nephrectomy
- Limited metastatic disease, as evidenced by any renal primary (T1 > 3 cm, any T2, T3, or T4) appropriate for cytoreductive nephrectomy
- Isolated abdominal/pelvic recurrence with limited metastatic burden (minimum size > 2 cm) appropriate for metastasectomy
- No known brain metastasis
- Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis
PATIENT CHARACTERISTICS:
- Eastern Cooperative Oncology Group performance status 0-1
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alanine aminotransferase and Aspartate aminotransferase ≤ 2.5 times ULN (≤ 5 times ULN with liver involvement)
- Creatinine ≤ 1.5 times ULN
- Estimated glomerular filtration rate > 30 mL/min (for patients receiving Gd-enhanced MRI)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to, during (men and women), and for at least 3 months after (men) completion of study therapy
- Adequate cardiac and pulmonary status for operative therapy
- No active clinically serious infection > CTCAE grade 2
- No known HIV, hepatitis B, or hepatitis C infections
- No serious non-healing wound, ulcer, or bone fracture
- No significant traumatic injury within the past 4 weeks
- No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within the past 4 weeks
- No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
- No history of an uncontrolled bleeding disorder including, but not limited to, any of the following:
- Bleeding diathesis
- Coagulopathy
- No cardiac disease or condition including, but not limited to, any of the following:
- New York Heart Association class II-IV congestive heart failure
- Unstable angina (anginal symptoms at rest)
- New onset angina beginning within the last 3 months
- Myocardial infarction within the past 6 months
- Cardiac ventricular arrhythmias requiring antiarrhythmic therapy
- No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical management
- No thrombolic or embolic events within the past 6 months (e.g., cerebrovascular accident including transient ischemic attacks)
- No condition that impairs the ability to swallow whole pills
- No malabsorption problem
- No contraindication to MRI, including, but not limited to, any of the following:
- Ferromagnetic implants
- Dental work
- Pacemakers
- Metallic implants
- Severe claustrophobia which precludes closed MRI testing
- No known or suspected allergy to sorafenib tosylate
- No contraindication or allergy to gadolinium (e.g., end stage renal disease requiring hemodialysis)
- No intercurrent illness or situation which, in the judgment of the investigator, would affect assessments of clinical status and study endpoints significantly
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 4 weeks since prior major surgery or open biopsy
- No prior therapy with tyrosine kinase or vascular endothelial growth factor inhibitors (e.g., sunitinib malate, sorafenib, or bevacizumab)
- No concurrent Hypericum perforatum (St. John's wort) or rifampin
- No concurrent use of illicit drugs or other substances that may, in the opinion of the investigator, have a reasonable chance of contributing to toxicity or interfering with study results
Trial locations and contacts
1 site in 1 country.
United States1 site
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
About this study
Official title: Correlation of Pathologic Findings After Neo-adjuvant Sorafenib With Results of Diffusion-Weighted Magnetic Resonance Imaging in Patients With Locally Advanced or Metastatic Clear Cell Renal Cell Carcinoma
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sorafenib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This clinical trial is studying how well sorafenib works in treating patients with locally advanced or metastatic kidney cancer.
Read the detailed description
OBJECTIVES:
Primary
- To demonstrate the feasibility and safety of sorafenib tosylate when given prior to nephrectomy or metastasectomy.
- To evaluate the ability of diffusion-weighted magnetic resonance imaging (DW-MRI) to detect early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions during neoadjuvant therapy with sorafenib tosylate.
- To correlate early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions with pathologic and clinical findings at the time of nephrectomy or metastasectomy.
- To evaluate the ability of changes in DW-MRI to predict subsequent favorable response to treatment (complete or partial response or stable disease) after 4 weeks of therapy.
OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients then undergo a nephrectomy or metastasectomy in week 5. Patients with residual metastatic disease may continue sorafenib tosylate twice daily and undergo a diffusion-weighted MRI (DW-MRI) every 8 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo a DW-MRI of the abdomen and pelvis at baseline and prior to week 5 to evaluate microstructure tumor changes and to allow for prediction of sorafenib tosylate benefit. DW-MRI results are correlated with surgical and pathologic findings obtained at week 5.
Resected tumor tissue are analyzed for vascular density and to distinguish apoptotic cell death from necrotic cell death via immunohistochemistry and to measure apoptotic cell death via TUNEL assay.
After completion of study treatment, patients are followed every 3 months for 2 years.
- Being tested
- Sorafenib
- Keywords
- clear cell renal cell carcinoma, hereditary clear cell renal cell carcinoma, recurrent renal cell cancer, stage I renal cell cancer, stage II renal cell cancer, stage III renal cell cancer, stage IV renal cell cancer
- Medical subject headings
- Kidney Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called Nexavar
400mg by mouth twice daily for 28 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib | Experimental | Eligible patients undergo pre-treatment DW-MRI of the abdomen and pelvis. Patient then receive Sorafenib 400mg orally twice daily on days 1-28. Following completion of 28 days of sorafenib, patients obtain a second DW-MRI. Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change in Difference in Apparent Diffusion Coefficient Between Baseline and Week 5
Mean Difference in Apparent Diffusion Coefficient [Time Frame: Baseline and Week 5] To assess whether changes in the apparent diffusion coefficient (ADC) during neoadjuvant sorafenib treatment are detectable in locally advanced or metastatic kidney cancer. The ADC value will be calculated at baseline (within 28 days of initiating sorafenib) and Week 5, and the mean difference will be calculated. The percent change between this mean difference is reported. Week 5 ADC value minus baseline ADC value/divided by baseline ADC value was calculated for each participant. Apparent diffusion coefficient (ADC), obtained by measuring diffusion values at magnetic resonance imaging (MRI), is a measure of water mobility. Lower values correspond to tumor and higher values are consistent with cysts. With sorafenib therapy, the amount of free water may increase in a lesion due to necrosis, and as a result the ADC may increase in value.
Measured: Baseline and week 5
Change in Tumor Size From Baseline to Approximately 29-34 Days After Completion of Neoadjuvant Sorafenib Treatment
Tumors were measured at baseline and approximately 29-34 days after completion of neoadjuvant treatment with sorafenib (just prior to surgery). Tumors were assessed by RECIST response criteria.
Measured: Just prior to study week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2008 (estimated)
- Study startJul 2008
- Primary completionOct 2011
- Study completionSep 2013
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hereditary Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Timothy M. Kuzel, MD, Principal investigator, Robert H. Lurie Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00727532
- Sponsor's protocol ID
- NU 07U1
- Other IDs
- P30CA060553, NU-IRB-STU00003123
- Status last verified
- Oct 2018
- First submitted
- 1 Aug 2008
- Last updated
- 3 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation of Pathologic Findings After Neo-adjuvant Sorafenib With Results of Diffusion-Weighted Magnetic Resonance Imaging in Patients With Locally Advanced or Metastatic Clear Cell Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00727532
- Acronym / sponsor ID
- NU 07U1
- Keywords
- clear cell renal cell carcinoma, hereditary clear cell renal cell carcinoma, recurrent renal cell cancer, stage I renal cell cancer, stage II renal cell cancer, stage III renal cell cancer, stage IV renal cell cancer
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2008
- Primary completion
- Oct 2011 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 4 Aug 2008 (estimated)
- Results
- Posted 3 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sorafenib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This clinical trial is studying how well sorafenib works in treating patients with locally advanced or metastatic kidney cancer.
Detailed description
OBJECTIVES:
Primary
- To demonstrate the feasibility and safety of sorafenib tosylate when given prior to nephrectomy or metastasectomy.
- To evaluate the ability of diffusion-weighted magnetic resonance imaging (DW-MRI) to detect early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions during neoadjuvant therapy with sorafenib tosylate.
- To correlate early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions with pathologic and clinical findings at the time of nephrectomy or metastasectomy.
- To evaluate the ability of changes in DW-MRI to predict subsequent favorable response to treatment (complete or partial response or stable disease) after 4 weeks of therapy.
OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients then undergo a nephrectomy or metastasectomy in week 5. Patients with residual metastatic disease may continue sorafenib tosylate twice daily and undergo a diffusion-weighted MRI (DW-MRI) every 8 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo a DW-MRI of the abdomen and pelvis at baseline and prior to week 5 to evaluate microstructure tumor changes and to allow for prediction of sorafenib tosylate benefit. DW-MRI results are correlated with surgical and pathologic findings obtained at week 5.
Resected tumor tissue are analyzed for vascular density and to distinguish apoptotic cell death from necrotic cell death via immunohistochemistry and to measure apoptotic cell death via TUNEL assay.
After completion of study treatment, patients are followed every 3 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib | Experimental | Drug: SorafenibEligible patients undergo pre-treatment DW-MRI of the abdomen and pelvis. Patient then receive Sorafenib 400mg orally twice daily on days 1-28. Following completion of 28 days of sorafenib, patients obtain a second DW-MRI. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| SorafenibAlso: Nexavar400mg by mouth twice daily for 28 consecutive days | Drug | Sorafenib |
Primary outcome
Percentage Change in Difference in Apparent Diffusion Coefficient Between Baseline and Week 5
Time frame: Baseline and week 5
Mean Difference in Apparent Diffusion Coefficient [Time Frame: Baseline and Week 5] To assess whether changes in the apparent diffusion coefficient (ADC) during neoadjuvant sorafenib treatment are detectable in locally advanced or metastatic kidney cancer. The ADC value will be calculated at baseline (within 28 days of initiating sorafenib) and Week 5, and the mean difference will be calculated. The percent change between this mean difference is reported. Week 5 ADC value minus baseline ADC value/divided by baseline ADC value was calculated for each participant. Apparent diffusion coefficient (ADC), obtained by measuring diffusion values at magnetic resonance imaging (MRI), is a measure of water mobility. Lower values correspond to tumor and higher values are consistent with cysts. With sorafenib therapy, the amount of free water may increase in a lesion due to necrosis, and as a result the ADC may increase in value.
Change in Tumor Size From Baseline to Approximately 29-34 Days After Completion of Neoadjuvant Sorafenib Treatment
Time frame: Just prior to study week 5
Tumors were measured at baseline and approximately 29-34 days after completion of neoadjuvant treatment with sorafenib (just prior to surgery). Tumors were assessed by RECIST response criteria.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Timothy M. Kuzel, MD principal investigator
Robert H. Lurie Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sorafenib in people with Hereditary Clear Cell Renal Cell Carcinoma and Kidney Cancer, run by Northwestern University at 1 site 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?
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: stopped early, as of the sponsor's last update on 3 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage Change in Difference in Apparent Diffusion Coefficient Between Baseline and Week 5 (time frame: Baseline and week 5). The study lists 2 primary outcomes in all. 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 3 May 2019.