A Phase II multi-center, non-randomized, open-label study of TKI258 in patients with either FGFR3 mutated or FGFR3 wild type advanced urothelial carcinoma. - ND

• Conditions: FGFR3 mutated or FGFR3 wild type advanced urothelial carcinoma.; MedDRA version: 9.1Level: LLTClassification code 10064467

• Registration Number: EUCTR2008-005870-11-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-01
• Last Update Posted: 10 December 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Patients with histological confirmation of transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis Locally advanced or metastatic disease 2. Archival tumor tissue available for Novartis designated FGFR3 mutational status analysis 3. Patients with documented progressive disease at baseline: progressive disease defined as new or progressive lesions on cross-sectional imaging 4. Patients with at least one measurable site of disease as defined by RECIST criteria that has not been previously irradiated 5. Previously treated with at least 1 but not more than 3 systemic cytotoxic regimens, with at least one of these regimens including at least one of the following: cisplatin, carboplatin, gemcitabine or taxane, administered in the perioperative or advanced setting and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or as part of a single regimen 6. Age ≥ 18 years 7. WHO Performance Status ≤ 2 8. Willing and able to take oral medication, comply with scheduled visits, treatment plan and laboratory tests 9. Signed and witnessed informed consent form obtained prior to any screening procedures 10. Required baseline laboratory values: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 [SI units 1.5 x 109/L] Platelets ≥ 100,000 cells/mm3 [SI units 100 x 109/L] Hemoglobin ≥ 9.0 g/dL [SI units 90 g/L] AST/SGOT and ALT/SGPT ≤ 3.0 x Upper Limit of Normal [ULN] (or AST/SGOT and ALT/SGPT ≤ 5 x ULN if abnormal liver function is due to tumor involvement of the liver) Bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x ULN Potassium within normal limits Sodium within normal limits Total Calcium (corrected for serum albumin) within normal limits Magnesium within normal limits Phosphorus within normal limits
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients with known brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases 2.Patients with history of another malignancy within the last five years prior to study entry,except cured basal cell carcinoma of the skin, excised carcinoma in situ of the cervix, or adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable 3.Patients who have received the last administration of an anti-cancer therapy, including:chemotherapy, immunotherapy, hormonal therapy, and targeted therapy, but excluding: nitrosourea, mitomycin-C, monoclonal antibodies, and radiation ≤ 14 days prior to starting study drug, or who have not recovered from side effects of such therapy 4.Patients who have received the last administration of nitrosourea or mitomycin-C ≤ 6weeks prior to starting study drug, or who have not recovered from the side effects of such therapy 5.Patients who received the last administration of an anti-cancer monoclonal antibody ≤ 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy 6.Patients who have received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy 7.Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy 8.Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: a.Impaired cardiac function or clinically significant cardiac diseases, (SEE THE PROTOCOL)b. Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month c. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TKI258 (e.g. ulcerative diseases, uncontrolled nausea, vomiting,diarrhea, malabsorption syndrome, or small bowel resection) d.Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) e.History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the investigator, would impair study compliance f. Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin g.Uncontrolled diarrhea ≥ CTCAE grade 2 h. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol i.Pregnant or breast-feeding women j.Women of child-bearing potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial and one month after the end of treatment. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore 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 24 consecutive months (i.e. who have had menses any time in

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the Overall Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) in patients with (FGFR3MUT) advanced urothelial carcinoma treated with TKI258 To determine the Overall Response Rate (ORR) as assessed by RECIST in patients with (FGFR3WT) advanced urothelial carcinoma treated with TKI258.;Secondary Objective: To determine Overall Response Rate (ORR) as per central assessment in both groups To determine Progression Free Survival (PFS) and Overall Survival (OS) in both groups To determine Disease Control Rate (DCR - Complete Response (CR), Partial Response (PR) and Stable Disease (SD) ≥16 weeks after start of TKI258 treatment) in both groups To characterize the safety and tolerability of TKI258 treatment;Primary end point(s): Overall Response (CR or PR) Rate. CR and PR will be defined according to RECIST (defined in Post-Text Supplement 1) as per local assessment.