E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is:
* To evaluate the objective response rate of the selected dose regimen out of 2 possible dose regimens (Regimen 1: 10 mg dose once daily, 7 days on/7 days off; and regimen 2: 6 mg dose, once daily; for 28 day cycles) in subjects with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
* To evaluate the objective response rate in chemo-refractory subjects
* To evaluate the progression-free survival (PFS), duration of response, and overall survival in all and chemo-refractory subjects
*To evaluate the response rate in biomarker-specific subgroups (translocations versus mutations)
* To evaluate the safety and pharmacokinetics of JNJ-42756493 at the 2 dose regimens |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 [bhCG]) at Screening for women of child bearing potential who are sexually active
- Must have shown disease progression according to RECIST,
version 1.1, following prior chemotherapy for metastatic or
surgically unresectable urothelial cancer. Subjects who received
neoadjuvant or adjuvant chemotherapy and showed disease
recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These subjects will be
referred to as chemorefractory
subjects. (Subjects who have shown disease progression according to RECIST, version 1.1 following prior treatment with antiProgrammed
deathligand 1 (anti PDL1/PD1) antibodies are also eligible) |
|
E.4 | Principal exclusion criteria |
- Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and
mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 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, breastfeeding, 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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants with Best Overall Response |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Progression-free survival
2. Duration of Response
3. Overall survival
4. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
5. Biomarker Assessment
6. Plasma Concentration of JNJ 42756493
7. Plasma Clearance of JNJ 42756493
8. Volume of Distribution of JNJ 42756493 |
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E.5.2.1 | 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)
3. From the date of the first dose of study drug until death (up to 3yrs 9m)
4. Screening up to end of study (approx 3yrs 9m)
5/6/7/8. Baseline up to end of study (approx 3 years 9 months)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Moldova, Republic of |
Romania |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is defined as approximately 12 months after last subject is enrolled or anytime the Sponsor terminates the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |