A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects with Metastatic or Surgically Unresectable Urothelial Cancer with FGFR Genomic Alterations
- Conditions
- rothelial cancerMedDRA 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-IT
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 165
- 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
- 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 Timepoint(s) of evaluation of this end point: 1 year;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
- 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>