A Phase 3 Study of Erdafitinib Compared with Vinflunine or Docetaxel or Pembrolizumab in Subjects with Advanced Urothelial Cancer and Selected FGFR Gene Aberrations
- Conditions
- Advanced Urothelial Cancerbladder cancer10004994
- Registration Number
- NL-OMON55515
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
1. >=18 years of age (or the legal age of consent in the jurisdiction in which
the study is
taking place)
2. Histologic demonstration of transitional cell carcinoma of the urothelium.
Minor components (<50% overall) of variant histology such as glandular or
squamous differentiation, or evolution to more aggressive phenotypes such as
sarcomatoid or micropapillary change are acceptable
3. Criterion amended per Amendment 2:
3.1 Metastatic or surgically unresectable urothelial cancer
4. Documented progression of disease, defined as any progression that requires
a change in
treatment, prior to randomization
5. Criterion modified per Amendment 5:
5.3 Cohort 1: Prior treatment with an anti-PD-(L)1 agent as monotherapy or as
combination therapy; no more than 2 prior lines of systemic treatment. Prior
treatment with an anti-PD-(L)1 agent could have been given as neo-adjuvant,
adjuvant, or in metastatic line of treatment as frontline or maintenance
therapy, as follows:
* together with chemotherapy or as maintenance therapy
* together with chemotherapy in metastatic setting
* for superficial cancer (early disease/non-muscle invasive bladder cancer),
OR in neo-adjuvant OR adjuvant setting. If these subjects did not relapse
within a year of their last dose of anti-PD-(L)1, this will not be counted as a
prior line of systemic treatment. These subjects will however still be eligible
only for Cohort 1.
Cohort 2: No prior treatment with an anti-PD-(L)1 agent; only 1 line of prior
systemic
treatment.
Note: Subjects who received neoadjuvant or adjuvant chemotherapy or
immunotherapy and showed disease progression within 12 months of the last dose
are considered to have received systemic therapy in the metastatic setting.
6. Subjects must meet appropriate molecular eligibility criteria (as determined
by central laboratory screening or local or by local historical test results
(from tissue or blood) performed at a Clinical Laboratory Improvement
Amendments (CLIA)-certified or regional equivalent laboratory using the
following methods: local next-generation sequencing (NGS), direct digital
counting methods, or the Qiagen Therascreen FGFR Rotor-Gene Q (RGQ) reverse
transcription polymerase chain reaction (RT-PCR) test.
Tumors must have at least 1 of the following translocations: FGFR2-BICC1,
FGFR2-CASP7, FGFR3-TACC3, FGFR3-BAIAP2L1; or 1 of the following FGFR3 gene
mutations: R248C, S249C, G370C, Y373C.
7. ECOG performance status Grade 0, 1, or 2 (Attachment 1)
8. Criterion amended per Amendment 2:
8.1 Criterion modified per Amendment 3:
8.2.Criterion modified per Amendment 4:
8.3 Criterion modified per Amendment 5:
8.4 Adequate bone marrow, liver, and renal function:
a. Bone marrow function (without the support of cytokines or
erythropoiesis-stimulating
agent in preceding 2 weeks):
* Absolute neutrophil count (ANC) >1,500/mm3
* Platelet count >75,000/mm3 (>=100,000/mm3 for Cohort 1 subjects at sites
choosing vinflunine chemotherapy)
* Hemoglobin >8.0 g/dL (without transfusion or demonstrate stability, ie; no
significant decline in hemoglobin, for 2 weeks after transfusion)
b. Liver function:
* Total bilirubin <=1.5 x institutional upper limit of normal (ULN) OR direct
bilirubin <=ULN for subjects with total bilirubin levels >1.5xULN [<=1xULN for
Cohort 1 sub
1. Treatment with any other investigational agent or participation in another
clinical study with therapeutic intent within 30 days prior to randomization.
2. Criterion amended per Amendment 2:
2.1 Criterion modified per Amendment 3:
2.2 Active malignancies (ie, requiring treatment change in the last 24 months).
The
only allowed exceptions are:
* urothelial cancer.
* skin cancer treated within the last 24 months that is considered completely
cured.
* localized prostate cancer with a Gleason score of 6 (treated within the last
24 months or untreated and under surveillance).
* localized prostate cancer with a Gleason score of 3+4 that has been treated
more
than 6 months prior to full study screening and considered to have a very low
risk
of recurrence.
3. Symptomatic central nervous system metastases.
4. Received prior FGFR inhibitor treatment.
5. Known allergies, hypersensitivity, or intolerance to erdafitinib or its
excipients
6. Criterion amended per Amendment 2:
6.1 Criterion modified per Amendment 3.
6.2 Current central serous retinopathy (CSR) or retinal pigment epithelial
detachment
of any grade.
7. History of uncontrolled cardiovascular disease including:
a. unstable angina, myocardial infarction, ventricular fibrillation, Torsades de
Pointes, cardiac arrest, or known congestive heart failure Class III-V
(Attachment 3) within the preceding 3 months; cerebrovascular accident or
transient ischemic attack within the preceding 3 months.
b. QTc prolongation as confirmed by triplicate assessment at screening
(Fridericia;
QTc >480 milliseconds).
c. Pulmonary embolism or other venous thromboembolism (VTE) within the
preceding 2 months.
8. Known active AIDS (human immunodeficiency virus (HIV) infection), unless the
subject has been on a stable anti-retroviral therapy regimen for the last 6
months or
more, has had no opportunistic infections in the last 6 months, and has CD4
count
>350.
9. Criterion amended per Amendment 3: 9.1 Known active hepatitis B or C
infection (unless polymerase chain reaction
[(PCR]-negative [according to local laboratory range] on all available tests
for the past
6 months).
10. Criterion amended per Amendment 3:
10.1 Not recovered from reversible toxicity of prior anticancer therapy (except
toxicities which are not clinically significant such as alopecia, skin
discoloration,
neuropathy, hearing loss).
11. Impaired wound healing capacity defined as skin/decubitus ulcers, chronic
leg ulcers,
known gastric ulcers, or unhealed incisions.
12. Major surgery within 4 weeks before randomization.
13. Criterion amended per Amendment 2: 13.1 Criterion modified per Amendment 3:
13.2 Any condition for which, in the opinion of the investigator, participation
would not be in the best interest of the subject (eg, compromise the
well-being) or that could prevent, limit, or confound the protocol-specified
assessments. Examples include ongoing active infection requiring systemic
therapy and uncontrolled ongoing medical conditions.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>The primary endpoint is overall survival (OS). Overall survival is measured<br /><br>from the date of randomization to the date of the subject*s death. If the<br /><br>subject is alive or the vital status is unknown, the subject will be censored<br /><br>at the date the subject was last known to be alive.</p><br>
- Secondary Outcome Measures
Name Time Method