Bladder CancerPhase 2NCT01732107
Dovitinib in BCG Refractory Urothelial Carcinoma With FGFR3 Mutations or Over-expression
A Phase 2 study testing Dovitinib in people with Bladder Cancer, run by Noah Hahn, M.D. at 3 sites in United States.
Trial summary
This trial will assess the 6-month complete response rate and toxicity profile of oral dovitinib therapy in BCG-refractory urothelial carcinoma patients with tumors with FGFR3 mutations or over-expression who are ineligible for or refusing cystectomy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Dovitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2013to 6 Mar 2017
- 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
- Histologically confirmed early stage urothelial carcinoma of the bladder defined as Ta, T1, or Tis stage.
- Presence of either an FGFR3 mutation or FGFR3 over-expression within bladder tumor tissue.
- Documented BCG-refractory disease defined as failure to achieve a tumor free state after at least 2 prior induction courses of intravesical BCG therapy.
- Medically unfit to undergo cystectomy or electively choosing to forego cystectomy
- Patients who give a written informed consent obtained according to local guidelines
Who cannot join
- Patients with muscle-invasive (i.e. T2, T3, T4), locally advanced non-resectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration.
- Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma.
- Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, clinically localized prostate cancer, biochemically relapsed non-metastatic prostate cancer (i.e., PSA only disease), or skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer)
- Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
- Patients who have received prior VEGFR-targeted or FGFR-targeted agents (i.e., sunitinib, pazopanib, sorafenib, bevacizumab, axitinib, etc.).
- Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
Show all 17Show fewer
- Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e., TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
- Uncontrolled hypertension defined by a systolic blood pressure (SBP) ≥ 160 mm Hg and/or d iastolic blood pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication(s)
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
- Patients who are currently receiving anti-coagulation treatment with therapeutic doses of warfarin. Full-dose anti-coagulation with low molecular weight heparin is permitted.
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
- Pregnant or breast-feeding women
- Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Oral, implantable, or injectable contraceptives that may be affected by cytochrome P450 interactions are not considered effective for this study. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug.
- Fertile males not willing to use contraception, as stated above
- Patients unwilling or unable to comply with the protocol
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Fox Chase Cancer Center Extramural Research Program
Rockledge, Pennsylvania, 19046
About this study
Official title: A Phase II Trial of Dovitinib in Bacillus Calmette-Guerin(BCG) Refractory Urothelial Carcinoma Patients With Tumor Fibroblast Growth Factor Receptor 3(FGFR3) Mutations or Over-expression: Hoosier Cancer Research Network GU12-157
This trial will assess the 6-month complete response rate and toxicity profile of oral dovitinib therapy in BCG-refractory urothelial carcinoma patients with tumors with FGFR3 mutations or over-expression who are ineligible for or refusing cystectomy.
Read the detailed description
OUTLINE: This is a multi-center study.
- Dovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. Day 12 assessments are intended to be performed on the last dosing day of the 2nd week in cycle 1 and cycle 2 and day 26 assessments are intended to be performed on the last dosing day of the 4th week in cycle 1 and cycle 2.
- Standard of Care: Cystoscopy with tumor biopsy, bladder biopsy, urine cytology
- Physician discretion: Anti-emetic medications and/or colony stimulating growth factors
ECOG performance status 0 - 2
Hematopoietic:
- White blood cell count (WBC) > 3.0 K/mm3
- Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
- Platelets ≥ 100 K/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
Hepatic:
- Serum total bilirubin: ≤ 1.5 x Upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3.0 x ULN
Renal:
- Serum creatinine ≤ 1.5 x ULN or serum creatinine > 1.5 - 3 x ULN if calculated creatinine clearance (CrCl) is ≥ 30 mL/min using the Cockcroft-Gault equation
Cardiovascular:
No impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of serious uncontrolled ventricular arrhythmias
- Clinically significant resting bradycardia
- LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA), < 45% or lower limit of normal (whichever is higher)
- Myocardial Infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)within 6 months prior to starting study drug
- Conditions
- Bladder Cancer
- Being tested
- Dovitinib
- Keywords
- Dovitinib, FGFR3 Mutations, BCG-Refractory Urothelial Carcinoma
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DovitinibDrug
Dovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. Day 12 assessments are intended to be performed on the last dosing day of the 2nd week in cycle 1 and cycle 2 and day 26 assessments are intended to be performed on the last dosing day of the 4th week in cycle 1 and cycle 2.
| Study group | Role | What they receive |
|---|---|---|
| Dovitinib | Experimental | Dovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. Receives: Drug: Dovitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine 6-Month Complete Response Rate
The 6-month complete response rate is defined as the proportion of patients treated with dovitinib with no evidence of any remaining urothelial carcinoma tumors of any T-stage (including Tis) present within the bladder as assessed by standard of care cystoscopic examination with transurethral resection of bladder tumor (TURBT) and urine cytology performed at 6 months after initiation of study therapy.
Measured: 6 months
Secondary outcomes (4)
Determine 1-Year Relapse-Free Survival Rate
The 1-year relapse free survival rate is defined as the proportion of patients treated with dovitinib with no evidence of any remaining urothelial carcinoma tumors at 12 months of follow-up.
Measured: 12 months
Determine Rate of Progression to Muscle-Invasive Stage
The rate of progression to muscle-invasive stage for dovitinib is defined as the proportion of patients with clinical or pathologic progression to muscle-invasive stages (i.e., T2-T4) at any time point on study.
Measured: 12 months
Determine 3-Month and 6-Month Partial Response Rates
The 3- and 6-month partial response rates are defined as the proportion of patients treated with persistent but reduced T-stage tumors on post-therapy TURBT (i.e., T1 ≥ Ta; T1+Tis ≥ T1).
Measured: 6 months
Characterize Treatment-related Toxicity Rates
Treatment-related toxicity rates will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All grade 3-4 adverse events and other adverse events occurring in more than 20% of patients are reported.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2012 (estimated)
- Study startMar 2013
- Primary completion6 Mar 2017
- Study completion6 Mar 2017
Why it stopped: Development of dovitinib was stopped.
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 Bladder CancerStudies of the same condition, open and under way.
- 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Noah Hahn, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Hoosier Cancer Research Network
- Responsible party
- Sponsor-investigator, Noah Hahn, M.D., Hoosier Cancer Research Network
- Investigators
- Noah Hahn, M.D., Study chair, Hoosier Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01732107
- Sponsor's protocol ID
- GU12-157
- Status last verified
- Jul 2022
- First submitted
- 19 Nov 2012
- Last updated
- 11 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Dovitinib in Bacillus Calmette-Guerin(BCG) Refractory Urothelial Carcinoma Patients With Tumor Fibroblast Growth Factor Receptor 3(FGFR3) Mutations or Over-expression: Hoosier Cancer Research Network GU12-157
- ClinicalTrials.gov ID
- NCT01732107
- Acronym / sponsor ID
- GU12-157
- Conditions
- Bladder Cancer
- Keywords
- Dovitinib, FGFR3 Mutations, BCG-Refractory Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Development of dovitinib was stopped.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Noah Hahn, M.D.University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Hoosier Cancer Research Network
- Study start
- Mar 2013 (actual)
- Primary completion
- 6 Mar 2017 (actual)
- Study completion
- 6 Mar 2017 (actual)
- First posted
- 22 Nov 2012 (estimated)
- Results
- Posted 22 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will assess the 6-month complete response rate and toxicity profile of oral dovitinib therapy in BCG-refractory urothelial carcinoma patients with tumors with FGFR3 mutations or over-expression who are ineligible for or refusing cystectomy.
Detailed description
OUTLINE: This is a multi-center study.
- Dovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. Day 12 assessments are intended to be performed on the last dosing day of the 2nd week in cycle 1 and cycle 2 and day 26 assessments are intended to be performed on the last dosing day of the 4th week in cycle 1 and cycle 2.
- Standard of Care: Cystoscopy with tumor biopsy, bladder biopsy, urine cytology
- Physician discretion: Anti-emetic medications and/or colony stimulating growth factors
ECOG performance status 0 - 2
Hematopoietic:
- White blood cell count (WBC) > 3.0 K/mm3
- Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
- Platelets ≥ 100 K/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
Hepatic:
- Serum total bilirubin: ≤ 1.5 x Upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3.0 x ULN
Renal:
- Serum creatinine ≤ 1.5 x ULN or serum creatinine > 1.5 - 3 x ULN if calculated creatinine clearance (CrCl) is ≥ 30 mL/min using the Cockcroft-Gault equation
Cardiovascular:
No impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of serious uncontrolled ventricular arrhythmias
- Clinically significant resting bradycardia
- LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA), < 45% or lower limit of normal (whichever is higher)
- Myocardial Infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)within 6 months prior to starting study drug
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dovitinib | Experimental | Drug: DovitinibDovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically confirmed early stage urothelial carcinoma of the bladder defined as Ta, T1, or Tis stage.
- Presence of either an FGFR3 mutation or FGFR3 over-expression within bladder tumor tissue.
- Documented BCG-refractory disease defined as failure to achieve a tumor free state after at least 2 prior induction courses of intravesical BCG therapy.
- Medically unfit to undergo cystectomy or electively choosing to forego cystectomy
- Patients who give a written informed consent obtained according to local guidelines
Key exclusion criteria (17 listed)
- Patients with muscle-invasive (i.e. T2, T3, T4), locally advanced non-resectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration.
- Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma.
- Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, clinically localized prostate cancer, biochemically relapsed non-metastatic prostate cancer (i.e., PSA only disease), or skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer)
- Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
- Patients who have received prior VEGFR-targeted or FGFR-targeted agents (i.e., sunitinib, pazopanib, sorafenib, bevacizumab, axitinib, etc.).
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 |
|---|---|---|
| DovitinibDovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. Day 12 assessments are intended to be performed on the last dosing day of the 2nd week in cycle 1 and cycle 2 and day 26 assessments are intended to be performed on the last dosing day of the 4th week in cycle 1 and cycle 2. | Drug | Dovitinib |
Primary outcome
Determine 6-Month Complete Response Rate
Time frame: 6 months
The 6-month complete response rate is defined as the proportion of patients treated with dovitinib with no evidence of any remaining urothelial carcinoma tumors of any T-stage (including Tis) present within the bladder as assessed by standard of care cystoscopic examination with transurethral resection of bladder tumor (TURBT) and urine cytology performed at 6 months after initiation of study therapy.
4 secondary outcomes
Determine 1-Year Relapse-Free Survival Rate
Time frame: 12 months
Determine Rate of Progression to Muscle-Invasive Stage
Time frame: 12 months
Determine 3-Month and 6-Month Partial Response Rates
Time frame: 6 months
Characterize Treatment-related Toxicity Rates
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Hoosier Oncology Group WebsiteLink provided by the sponsor.
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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.
Noah Hahn, M.D. study chair
Hoosier Cancer Research Network
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 Dovitinib in people with Bladder Cancer, run by Noah Hahn, M.D. 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 5 inclusion and 17 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 11 Jul 2022. 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 22 Aug 2018). 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?
Determine 6-Month Complete Response Rate (time frame: 6 months). 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 11 Jul 2022.