Renal Cell CarcinomaPhase 2NCT01253668

Brivanib Metastatic Renal Cell Carcinoma

A Phase 2 study testing Brivanib alaninate, Polymerase chain reaction and Iodine I 124 chimeric monoclonal antibody G250 in people with Renal Cell Carcinoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

This is a phase II study of an investigational agent, brivanib, in patients with refractory metastatic renal cell carcinoma. This study will evaluate the safety and effectiveness of brivanib in renal cell carcinoma, and explore the activity of this drug in this population to determine whether imaging and molecular… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Renal Cell Carcinoma
What is being tested?: Brivanib alaninate, Polymerase chain reaction and Iodine I 124 chimeric monoclonal antibody G250
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteUnited States
Study dates: Nov 2011to Sep 2013
Phase: Phase 2
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female adults with metastatic renal cell carcinoma
Patients will have tumors that bear a clear cell component that comprises greater than or equal to 50% of the tumor.
Disease must be measurable in accord with RECIST 1.1 guidelines.
Patients who have developed progressive disease or intolerance on treatment with sorafenib, sunitinib, bevacizumab, or pazopanib over a 60 day period who have not discontinued this therapy more than 100 days prior to study enrollment. Progressive disease per RECIST 1.1 guidelines will be preferred
Therapy with up to three prior systemic regimens will be allowed.
Patients may have been treated with any of the following: sorafenib, sunitinib, bevacizumab, pazopanib, temsirolimus, everolimus, interferon alpha, interleuken-2.

Show all 12Show fewer

Treatment with up to one prior regimen that included cytotoxic chemotherapy will be allowed.
Patients may have been treated with more than 1 antiangiogenic therapy (e.g., patients may have been treated with both sorafenib and sunitinib or sunitinib and bevacizumab, or sequential combinations that include pazopanib).
Life expectancy of at least 3 months
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Tumor tissue must be available for correlative studies.
Patients must consent to allow the acquisition of formalin-fixed paraffin-embedded (FFPE) material (block or unstained slides) by study personnel for performance of correlative tissue studies.

Who cannot join

Known brain metastases
Prior therapy with brivanib, or anti-FGFR (fibroblast growth factor receptor) therapy.
History of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism.
Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 4.0 Grade greater than 3 within 30 days prior to study entry.
Uncontrolled or significant cardiovascular disease.
QTc greater than 450 msec on two consecutive ECGs (Baseline ECG should be repeated if QTc is found to be greater than 450 msec.).

Show all 15Show fewer

Active infection, less than 7 days after completing systemic antibiotic therapy.
History of non-healing wounds or ulcers or bone fractures within 3 months of fracture.
Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks prior to study enrollment or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration)within 1 week prior to study enrollment.
Cytotoxic chemotherapy within 3 weeks, bevacizumab within 2 months, or radiation therapy within 2 weeks, other targeted therapies (e.g., sorafenib, sunitinib, temsirolimus, everolimus)within 2 days.
Inability to swallow tablets or untreated malabsorption syndrome.
Pre-existing thyroid abnormality with thyroid function that cannot be controlled with medication.
History of HIV
Patients with centrally cavitating lung lesions.
Patients requiring therapeutic anticoagulation with warfarin at baseline. However, prophylactic therapy with a low molecular weight heparin at baseline is acceptable.

Trial locations and contacts

1 site in 1 country.

United States1 site

Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Brivanib (BMS-582664, Brivanib Alaninate) in Treatment of Refractory Metastatic Renal Cell Carcinoma - A Phase II Pharmacodynamic and Baseline Biomarker Study

Read the detailed description

The primary objective of this clinical trial is to determine the efficacy of brivanib in the treatment of metastatic renal cell carcinoma in terms of progression-free survival (PFS) in patients who have progressed on treatment with sunitinib, sorafenib, bevacizumab, or pazopanib. The primary endpoint of the trial will be PFS at 16 weeks. The secondary objectives are to further examine the safety and tolerability profile of brivanib, to examine the efficacy of brivanib in this population in terms of best overall response, response rate, progression-free survival, and overall survival, to describe baseline and changes in I-cG250 PET/CT in relation to observed therapeutic effects, to describe novel baseline histologic features of these tumors in relation to observed therapeutic effects. Modalities will include Von Hippel-Lindau gene (VHL) and hypoxia-inducible factor 1 gene (HIF-1) expression assessment and a novel histo-cytometric assessment of the tumor microenvironment in terms of p-STAT3, p-ERK, Ki67, VEGFR2, FGFR1 expression, to describe changes in circulating collagen IV on brivanib in relation to therapeutic effects, to explore the relationship between single nucleotide polymorphisms in angiogenesis-related genes and the activity of brivanib in the treatment of these patients.

Conditions: Renal Cell Carcinoma
Being tested: Brivanib alaninate, Polymerase chain reaction, Iodine I 124 chimeric monoclonal antibody G250, Positron emission tomography/computed tomography, Protein expression analysis
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.

Brivanib alaninateDrug
Brivanib by mouth daily at a dose of 800mg.
Polymerase chain reactionGenetic
Also called PCR
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Iodine I 124 chimeric monoclonal antibody G250Other
Undergo 124I-cG250 PET/CT imaging (correlative studies)
Positron emission tomography/computed tomographyProcedure or surgery
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Protein expression analysisGenetic
Correlative studies
ImmunohistochemistryOther
Also called immunohistochemistry staining method
correlative studies

Study groups in NCT01253668
Study group	Role	What they receive
Arm 1	Experimental	Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity. Receives: Drug: Brivanib alaninate; Genetic: Polymerase chain reaction; Other: Iodine I 124 chimeric monoclonal antibody G250; Procedure: Positron emission tomography/computed tomography; Genetic: Protein expression analysis; Other: Immunohistochemistry

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression Free Survival (PFS)
All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.
Measured: 16 weeks

Secondary outcomes (9)

Best Overall Response Rated for Each Patients as Assessed by RECIST 1.1 Guidelines
The best overall radiographic response to therapy as measured and assessed using RECIST 1.1 guidelines will be captured for each research subject.
Measured: Every 8 weeks
Overall Survival
Will record deaths on study, and, to the extent possible, after the study follow-up period is completed for each patient, will be captured. Reason for death will be identified and recorded where possible.
Measured: Every 8 weeks
Change in Total Antibody Binding as Assessed by 124I-cG250 PET/CT Imaging (Correlative Studies)
Will determine the baseline and change in total antibody binding in lesions from baseline to the time on treatment that patients are assessed. The analysis dataset will be quantitated radiotracer uptake data obtained via I-cG250 PET/CT for all evaluable patients who complete the trial.
Measured: At baseline and 8 weeks
Response Rate for All Patients
Response Rate for all patients as assessed by RECIST 1.1 guidelines
Measured: Every 8 weeks
Molecular Markers
Molecular markers expressed in patient tumor specimens as assessed by IHC and histocytometry (e.g., VHL, HIF, p-STAT3, p-ERK, and Ki67, VEGFR2, and FGFR1) (correlative studies)
Measured: At baseline
Changes in Collagen IV Levels
Changes in collagen IV levels for each patient (correlative studies)
Measured: At baseline and week 3
Germline Polymorphisms and Assessment of Relationship to Toxicity and Clinical Outcome
Germline polymorphisms and assessment of relationship to toxicity and clinical outcome (correlative studies)
Measured: At baseline and week 3
Blood Pressure Data
Blood pressure data
Measured: At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
Toxicity as Assessed by NCI CTCAE Version 4.0
Toxicity as assessed by NCI CTCAE version 4.0
Measured: Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2011Sep 2013

First posted3 Dec 2010 (estimated)
Study startNov 2011
Primary completionSep 2013
Study completionSep 2013

Why it stopped: In November 2012, this study was permanently closed to new accrual at the request of the drug manufacturer (BMS), who decided not to pursue additional research activity in this patient population.

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 Renal Cell CarcinomaStudies of the same condition, open and under way.
More trials run by Abramson Cancer Center at Penn MedicineThe 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01253668
Sponsor's protocol ID: UPCC 04810
Status last verified: Mar 2021
First submitted: 30 Nov 2010
Last updated: 13 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Not yet recruitingObservational study
Federated Learning in Renal Tumor Model
Renal Tumors
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
Active, not recruiting
App-Based Mindfulness Intervention for the Improvement of Quality of Life in Patients With Metastatic Renal Cell Cancer
Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8
RecruitingPhase 3
A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)
Carcinoma, Renal Cell

All Renal Cell Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Brivanib (BMS-582664, Brivanib Alaninate) in Treatment of Refractory Metastatic Renal Cell Carcinoma - A Phase II Pharmacodynamic and Baseline Biomarker Study
ClinicalTrials.gov ID: NCT01253668
Acronym / sponsor ID: UPCC 04810
Conditions: Renal Cell Carcinoma
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: In November 2012, this study was permanently closed to new accrual at the request of the drug manufacturer (BMS), who decided not to pursue additional research activity in this patient population.
Enrolment: 10 participants (actual)
Lead sponsor: Abramson Cancer Center at Penn MedicineUniversity, hospital or other
Study start: Nov 2011 (actual)
Primary completion: Sep 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 3 Dec 2010 (estimated)
Results: Posted 19 Mar 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Arm 1	Experimental	Drug: Brivanib alaninate, Genetic: Polymerase chain reaction, Other: Iodine I 124 chimeric monoclonal antibody G250, Procedure: Positron emission tomography/computed tomography, Genetic: Protein expression analysis, Other: ImmunohistochemistryPatients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Male and female adults with metastatic renal cell carcinoma
Patients will have tumors that bear a clear cell component that comprises greater than or equal to 50% of the tumor.
Disease must be measurable in accord with RECIST 1.1 guidelines.
Patients who have developed progressive disease or intolerance on treatment with sorafenib, sunitinib, bevacizumab, or pazopanib over a 60 day period who have not discontinued this therapy more than 100 days prior to study enrollment. Progressive disease per RECIST 1.1 guidelines will be preferred
Therapy with up to three prior systemic regimens will be allowed.

Key exclusion criteria (15 listed)

Known brain metastases
Prior therapy with brivanib, or anti-FGFR (fibroblast growth factor receptor) therapy.
History of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism.
Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 4.0 Grade greater than 3 within 30 days prior to study entry.
Uncontrolled or significant cardiovascular disease.

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
Brivanib alaninateBrivanib by mouth daily at a dose of 800mg.	Drug	Arm 1
Polymerase chain reactionAlso: PCRUndergo 1241-cG250 PET/CT imaging (correlative studies)	Genetic	Arm 1
Iodine I 124 chimeric monoclonal antibody G250Undergo 124I-cG250 PET/CT imaging (correlative studies)	Other	Arm 1
Positron emission tomography/computed tomographyUndergo 1241-cG250 PET/CT imaging (correlative studies)	Procedure or surgery	Arm 1
Protein expression analysisCorrelative studies	Genetic	Arm 1
ImmunohistochemistryAlso: immunohistochemistry staining methodcorrelative studies	Other	Arm 1

Primary outcome

Progression Free Survival (PFS)
Time frame: 16 weeks
All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.

9 secondary outcomes

Best Overall Response Rated for Each Patients as Assessed by RECIST 1.1 Guidelines
Time frame: Every 8 weeks
Overall Survival
Time frame: Every 8 weeks
Change in Total Antibody Binding as Assessed by 124I-cG250 PET/CT Imaging (Correlative Studies)
Time frame: At baseline and 8 weeks
Response Rate for All Patients
Time frame: Every 8 weeks
Molecular Markers
Time frame: At baseline
Changes in Collagen IV Levels
Time frame: At baseline and week 3
Germline Polymorphisms and Assessment of Relationship to Toxicity and Clinical Outcome
Time frame: At baseline and week 3
Blood Pressure Data
Time frame: At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
Toxicity as Assessed by NCI CTCAE Version 4.0
Time frame: Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter

Results and safety

Results posted to the registry on 19 Mar 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1	0	0

Primary outcome: Progression Free Survival (PFS)

Time frame: 16 weeks

Population analysed: The study was terminated, and the PI has left the institution. Despite all possible efforts to contact the PI/study team members, no data are available to be reported.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: The study was terminated, and the PI has left the institution. Despite all possible efforts to contact the PI/study team members, no data are available to be reported.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): The study was terminated, and the PI has left the institution. Despite all possible efforts to contact the PI/study team members, no data are available to be reported.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Renal Cell Carcinoma

Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Not yet recruitingObservational study
Federated Learning in Renal Tumor Model
Renal Tumors
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
Active, not recruiting
App-Based Mindfulness Intervention for the Improvement of Quality of Life in Patients With Metastatic Renal Cell Cancer
Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8
RecruitingPhase 3
A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)
Carcinoma, Renal Cell

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.

Stephen Keefe, MD principal investigator

Abramson Cancer Center at Penn Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 12 inclusion and 15 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: stopped early, as of the sponsor's last update on 13 Apr 2021. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2021). 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?

Progression Free Survival (PFS) (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01253668.

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 13 Apr 2021.