Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)Phase 2NCT02459119
Study of Regorafenib for Urothelial Cancer Following Chemotherapy (UAB 1477)
A Phase 2 study testing Regorafenib in people with Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer), run by University of Alabama at Birmingham at 3 sites in United States.
Trial summary
This study will test how well Regorafenib controls disease progression in urothelial cancer (cancer occurring in the urinary bladder, ureters, or renal pelvis) following previous therapy with chemotherapy. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)
- What is being tested?
- Regorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2015to Apr 2020
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have pathologically or cytologically proven transitional cell carcinoma of the urothelium.
- Progressive disease after 1-3 prior chemotherapy regimens (perioperative chemotherapy within 12 months will be considered one regimen).
- Prior regimen must be within 6 months of registration
- Measurable disease by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-1
- Patients with metastatic (lymph node or distant metastasis, i.e. N+ or M1) or locally advanced unresectable (T4b) transitional cell carcinoma.
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- Age ≥19 years
- Life expectancy of at least 12 weeks (3 months)
- Subjects must be able to understand and be willing to sign the written informed consent form.
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
- Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
- Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
- Serum creatinine ≤ 1.5 x the ULN
- International normalized ratio (INR) less than or equal to 1.5 x ULN. (Subjects who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists.Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care.
- Platelet count >100,000/mm3, hemoglobin (Hb) >8 g/dL, absolute neutrophil count (ANC) 1500/mm3. The patient cannot be transfused in order to meet study entry criteria.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post- menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. The definition of adequate contraception will be based on the judgment of the investigator.
- Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form until at least 3 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
- Subject must be able to swallow and retain oral medication.
Who cannot join
- Component of small-cell cancer or sarcomatoid cancer
- Prior therapy with any systemic therapy (chemotherapy or biologic therapy) within twenty-eight days prior to study entry
- Patients must have recovered from toxicities from prior systemic anticancer treatment or local therapies.
- Patients who have undergone major surgery <4 weeks or minor surgery <2 weeks prior to registration. Wounds must be completely healed prior to study entry and patients recovered from all toxicities from surgery. Placement of a vascular access device is not considered major or minor surgery in this regard.
- Prior radiation therapy is allowed as long as the irradiated area was not the sole source of measurable disease and radiotherapy was completed with recovery from toxicity, at least three weeks prior to enrollment. If the irradiated area is the only site of disease, there must be evidence of progressive disease.
- Uncontrolled central nervous system (CNS) metastases (previously treated with radiation and off steroids is acceptable).
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- Patient with active or uncontrolled infection.
- Recent or active bleeding diathesis or arterial vascular event within 4 weeks.
- Pregnant or nursing (Fertile patients must use effective contraception during and for up to 3 months after completion of study treatment.)
- Patients may not be receiving any other investigational agents.
- Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure >90 mm Hg on repeated measurement) despite optimal medical management.
- Active or clinically significant cardiac disease including:
- Congestive heart failure - New York Heart Association (NYHA) Class II.
- Active coronary artery disease.
- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
- Unstable angina (angina symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
- Evidence or history of bleeding diathesis or coagulopathy.
- Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
- Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment within 6 months of informed consent.
- Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from breast cancer except cervical cancer in-situ, treated localized basal cell carcinoma, Gleason score 6 prostate cancer or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments for another malignancy must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form).
- Patients with pheochromocytoma.
- Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
- Ongoing infection >Grade 2 NCI-CTCAE v4.0.
- Symptomatic metastatic brain or meningeal tumors.
- Presence of a non-healing wound, non-healing ulcer, or bone fracture.
- Renal failure requiring hemo-or peritoneal dialysis.
- Dehydration Grade >1 NCI-CTCAE v4.0.
- Patients with seizure disorder requiring medication.
- Persistent proteinuria greater than or equal to Grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample).
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
- Pleural effusion or ascites that causes respiratory compromise (≥ NCI- CTCAE version 4.0 Grade 2 dyspnea).
- History of organ allograft (including corneal transplant).
- Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.
- Any malabsorption condition.
- Women who are pregnant or breast-feeding.
- Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Cleveland Clinic
Cleveland, Ohio, 44195
Wayne State University
Detroit, Michigan, 48201-2013
About this study
Official title: A Multicenter, Non-Randomized, Phase II Study of Regorafenib for Advanced Urothelial Cancer Following Prior Chemotherapy
This study will test how well Regorafenib controls disease progression in urothelial cancer (cancer occurring in the urinary bladder, ureters, or renal pelvis) following previous therapy with chemotherapy.
Read the detailed description
Advanced urothelial carcinoma (UC) has a poor long-term prognosis. The disease has not seen improved outcomes despite research efforts in over two decades. Novel therapeutic options are needed. Regorafenib is a novel oral multikinase inhibitor but is more potent than a similar multikinase inhibitor drug that treats advanced renal cell carcinoma and hepatocellular carcinoma. Regorafenib has been shown to have a broader capacity to inhibit blood supply to tumor sources.
This trial evaluates a proof-of-concept using Regorafenib in patients with metastatic progressive urothelial carcinoma following chemotherapy but still have a high level of activity performance in their daily living. The initial dose of Regorafenib will be 120 mg daily and then be escalated to 160 mg daily before gradually tapering.
- Being tested
- Regorafenib
- Keywords
- urothelial cancer, Regorafenib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Regorafenib will be packaged as 40 mg tablets in a bottle. Patients will be instructed to maintain a daily medication calendar.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | Regorafenib will be administered orally to all patients on study. The drug will be taken once a day for 3 of every 4 week cycle (3 weeks on/1 week off). The dose is 120 mg once daily for the first cycle, then 160 mg once daily from the second cycle if no significant Regorafenib-associated toxicities occur during the first cycle. Drug dosage may be modified if toxicities occur. Patients will undergo up to 4 cycles of treatment and may continue on additional at the discretion of the investigator. Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Progression-free Survival at 6 Months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Death is also considered as progression in the analysis.
Measured: Baseline to 6 months following start of treatment
Secondary outcomes (4)
Disease Response Rate
The number of participants showing response at first restaging scan after the start of study treatment. The response will be assessed using tumor measurements which will be documented through CT scans, magnetic resonance imaging (MRI), and x-rays using the Response Evaluation Criteria in Solid Tumors (RECIST). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."
Measured: Every 8 weeks until the time of disease progression upto 2 years
Overall Survival
Length of subject survival after starting study treatment
Measured: Baseline to 3 years
Rate of Progression-free Survival
Duration of time from the start of treatment to time of progression or death, whichever comes first.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: From start of treatment to time of progression or death, assessed up to 6 months
Number of Participants With Adverse Events
The Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 will be used for assessment of toxicities.
Measured: At the end of first treatment until 6 months following last treatment, an expected average of 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2015 (estimated)
- Study startMay 2015
- Primary completionFeb 2019
- Study completionApr 2020
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 Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)Studies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
- Responsible party
- Principal investigator, Lisle Nabell, University of Alabama at Birmingham
- Investigators
- Lisle Nabell, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02459119
- Sponsor's protocol ID
- F150302002 (UAB 1477)
- Status last verified
- Jul 2020
- First submitted
- 26 May 2015
- Last updated
- 6 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Non-Randomized, Phase II Study of Regorafenib for Advanced Urothelial Cancer Following Prior Chemotherapy
- ClinicalTrials.gov ID
- NCT02459119
- Acronym / sponsor ID
- F150302002 (UAB 1477)
- Keywords
- urothelial cancer, Regorafenib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
- Study start
- May 2015
- Primary completion
- Feb 2019 (actual)
- Study completion
- Apr 2020 (actual)
- First posted
- 1 Jun 2015 (estimated)
- Results
- Posted 15 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test how well Regorafenib controls disease progression in urothelial cancer (cancer occurring in the urinary bladder, ureters, or renal pelvis) following previous therapy with chemotherapy.
Detailed description
Advanced urothelial carcinoma (UC) has a poor long-term prognosis. The disease has not seen improved outcomes despite research efforts in over two decades. Novel therapeutic options are needed. Regorafenib is a novel oral multikinase inhibitor but is more potent than a similar multikinase inhibitor drug that treats advanced renal cell carcinoma and hepatocellular carcinoma. Regorafenib has been shown to have a broader capacity to inhibit blood supply to tumor sources.
This trial evaluates a proof-of-concept using Regorafenib in patients with metastatic progressive urothelial carcinoma following chemotherapy but still have a high level of activity performance in their daily living. The initial dose of Regorafenib will be 120 mg daily and then be escalated to 160 mg daily before gradually tapering.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: RegorafenibRegorafenib will be administered orally to all patients on study. The drug will be taken once a day for 3 of every 4 week cycle (3 weeks on/1 week off). The dose is 120 mg once daily for the first cycle, then 160 mg once daily from the second cycle if no significant Regorafenib-associated toxicities occur during the first cycle. Drug dosage may be modified if toxicities occur. Patients will undergo up to 4 cycles of treatment and may continue on additional at the discretion of the investigator. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have pathologically or cytologically proven transitional cell carcinoma of the urothelium.
- Progressive disease after 1-3 prior chemotherapy regimens (perioperative chemotherapy within 12 months will be considered one regimen).
- Prior regimen must be within 6 months of registration
- Measurable disease by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-1
Key exclusion criteria (38 listed)
- Component of small-cell cancer or sarcomatoid cancer
- Prior therapy with any systemic therapy (chemotherapy or biologic therapy) within twenty-eight days prior to study entry
- Patients must have recovered from toxicities from prior systemic anticancer treatment or local therapies.
- Patients who have undergone major surgery <4 weeks or minor surgery <2 weeks prior to registration. Wounds must be completely healed prior to study entry and patients recovered from all toxicities from surgery. Placement of a vascular access device is not considered major or minor surgery in this regard.
- Prior radiation therapy is allowed as long as the irradiated area was not the sole source of measurable disease and radiotherapy was completed with recovery from toxicity, at least three weeks prior to enrollment. If the irradiated area is the only site of disease, there must be evidence of progressive 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 |
|---|---|---|
| RegorafenibRegorafenib will be packaged as 40 mg tablets in a bottle. Patients will be instructed to maintain a daily medication calendar. | Drug | Regorafenib |
Primary outcome
Number of Participants With Progression-free Survival at 6 Months
Time frame: Baseline to 6 months following start of treatment
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Death is also considered as progression in the analysis.
4 secondary outcomes
Disease Response Rate
Time frame: Every 8 weeks until the time of disease progression upto 2 years
Overall Survival
Time frame: Baseline to 3 years
Rate of Progression-free Survival
Time frame: From start of treatment to time of progression or death, assessed up to 6 months
Number of Participants With Adverse Events
Time frame: At the end of first treatment until 6 months following last treatment, an expected average of 10 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Lisle Nabell, MD principal investigator
University of Alabama at Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib in people with Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer), run by University of Alabama at Birmingham at 3 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 19 inclusion and 38 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 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 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 15 Apr 2020). 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?
Number of Participants With Progression-free Survival at 6 Months (time frame: Baseline to 6 months following start of treatment). 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 6 Aug 2020.