Dovitinib in BCG Refractory Urothelial Carcinoma With FGFR3 Mutations or Over-expression

NCT01732107 | Terminated Phase 2 Results DMC

• 1 other identifier: GU12-157
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Bladder Cancer

Keywords

Dovitinib; FGFR3 Mutations; BCG-Refractory Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (4)

• Determine 1-Year Relapse-Free Survival Rate

  12 months

• Determine Rate of Progression to Muscle-Invasive Stage

  12 months

• Determine 3-Month and 6-Month Partial Response Rates

  6 months

• Characterize Treatment-related Toxicity Rates

  12 months

Other Outcomes (7)

• Characterize Pre- and Post-treatment Bladder Tumor FGFR Pathway Phosphorylation Changes.

  12 months

• Characterize Associations Between Pre-treatment Germline, FGFR Single-nucleotide Polymorphisms (SNPs) and Post-treatment 6-month Complete Response Rate and 1-year Relapse Free Survival Rate in Patients Treated With Dovitinib.

  12 months

• Characterize Pre- and Post-treatment VEGFR Pathway Phosphorylation Changes as Assessed by Bladder Tumor Tissue Immunohistochemistry.

  12 months

Study Arms (1)

Dovitinib

EXPERIMENTAL

Dovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule.

Drug: Dovitinib

Interventions

Dovitinib DRUG

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.

Dovitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Noah Hahn, M.D.: lead
• Novartis Pharmaceuticals: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (3)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Fox Chase Cancer Center Extramural Research Program

Rockledge, Pennsylvania, 19046, United States

Location

Related Links

• Hoosier Oncology Group Website

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Clinical Data Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Noah Hahn, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: March 1, 2013
• Primary Completion: March 6, 2017
• Study Completion: March 6, 2017
• Last Updated: July 11, 2022
• Results First Posted: August 22, 2018

Record last verified: 2022-07

Locations

US (3)