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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Apr 2015 → ongoing

Decision date (initial)

2024-02-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Research & Development, LLC

External identifiers

EU CT number

2023-510273-34-00

EudraCT number

2014-002408-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Safety, Pharmacodynamic, Pharmacokinetic, Efficacy

To evaluate the objective response rate (complete response [CR]+ partial response [PR]) of the selected dose regimen in subjects with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
To evaluate the effects of repeated dosing of erdafitinib on the single-dose pharmacokinetics (PK) of midazolam (sensitive CYP3A4 substrate) and metformin (sensitive OCT2 substrate) in FGFR-eligible subjects with an unresectable, locally advanced, or metastatic solid tumor malignancy.

Conditions and MedDRA coding

Urothelial cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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
2. Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
3. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2
4. Must have adequate bone marrow, liver, and renal function as described in protocol
5. Negative pregnancy test (urine or serum beta human chorionic gonadotropin [bhCG]) at Screening for women of child bearing potential who are sexually active
6. 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)
7. Subjects with target FGFR mutations or FGFR gene fusions are eligible for enrollment in the substudy, as determined by local screening.
8. Subject (or his/her legally acceptable representative) must sign the informed consent documents indicating that they understand the purpose of procedures required for the DDI substudy and continuation of treatment until disease progression and are willing to participate in the study.

Exclusion criteria 9

1. 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
2. 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
3. Has a history of or current uncontrolled cardiovascular disease
4. 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.
5. 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)
6. Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade.
7. Medications known to induce or inhibit CYP3A or CYP2C9, or inhibit OCT2 must be discontinued or substituted 1 week prior to the first intake of the probe drugs, or must be temporarily interrupted during the course of the DDI substudy
8. Use of midazolam and metformin from 2 weeks before the first intake of probe drugs (for DDI purpose on Day -2 or Day -1), and until the last PK sample is collected on Study Day 15 (last 24-hour PK sampling).
9. Known contraindication to the use of metformin and/or midazolam, based on the local prescribing information.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of Participants with Best Overall Response
2. The endpoints are PK parameters for midazolam and its metabolite (1-OH-midazolam), and for metformin (in the absence or presence of erdafitinib) including but not limited to Cmax, tmax, AUClast, and AUC∞.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen Cilag International

Sponsor organisation

Janssen Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Third parties 1

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications