Dovitinib in BCG Refractory Urothelial Carcinoma With FGFR3 Mutations or Over-expression
Condition: Bladder Cancer
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Dovitinib
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Dovitinib; FGFR3 Mutations; BCG-Refractory Urothelial Carcinoma

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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

          -  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