An Efficacy and Safety Study of JNJ-42756493 in Participants with Urothelial Cancer

Phase 1

Conditions: rothelial cancer
MedDRA version: 18.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-002408-26-FR

Lead Sponsor: Janssen-Cilag International NV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 165

Inclusion Criteria

- Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
- Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2
- Must have adequate bone marrow, liver, and renal function as described in protocol
- Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 115

Exclusion Criteria

- Received chemotherapy, targeted therapies, definitive radiotherapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted
- Has persistent phosphate level greater than upper limit of normal (ULN) during
screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management
- Has a history of or current uncontrolled cardiovascular disease
- Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug
- Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is:<br>* To evaluate the objective response rate of the selected dose regimen out of 2 possible dose regimens (Regimen 1: 10 mg dose, 7 days on/7 days off; and regimen 2: 6 mg dose, 21 days on/7 days off) in subjects with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.;Secondary Objective: The secondary objectives of the study are:<br>* To evaluate the objective response rate in chemo-refractory subjects<br>* To evaluate the progression-free survival (PFS), duration of response, and overall survival in all and chemo-refractory subjects<br>To evaluate the response rate in biomarker-specific subgroups (translocations versus mutations)<br> To evaluate the safety and pharmacokinetics of JNJ-42756493 at the 2 dose regimens;Primary end point(s): Percentage of Participants with Best Overall Response;Timepoint(s) of evaluation of this end point: 1 year

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Progression-free survival<br>2. Duration of Response<br>3. Overall survival<br>4. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)<br>5. Biomarker Assessment<br>6. Plasma Concentration of JNJ 42756493<br>7. Plasma Clearance of JNJ 42756493<br>8. Volume of Distribution of JNJ 42756493;Timepoint(s) of evaluation of this end point: 1/2. From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (approx 3yrs 9m)<br>3. From the date of the first dose of study drug until death (up to 3yrs 9m)<br>4. Screening up to end of study (approx 3yrs 9m)<br>5/6/7/8. Baseline up to end of study (approx 3 years 9 months)<br>

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