The primary objective of this study is to evaluate the objective response rate (ORR) of INCB054828 as a monotherapy in the treatment of metastatic or surgically unresectable urothelial carcinoma harboring FGF/FGFR 3 mutations or fusions. The…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Objective response rate in subjects with FGFR3 mutations or fusions based on
central genomics laboratory results and INCB054828
administered using a continuous dose regimen (Cohort A-CD). Response will be
based on review of scans by a centralized radiological review committee.
Secondary outcome
The secondary endpoints of this study include:
* Objective response rate in all subjects with FGFR3 mutations or fusions based
on central genomics laboratory results and using an intermittent
dose regimen (Cohort A-ID). Response will be based on review of scans by a
centralized radiological review committee.
* Objective response rate in subjects with FGFR3 mutations or fusions based on
central genomics laboratory results and using a continuous
dose regimen (Cohort A-CD) and intermittent dose regimen (Cohort A-ID).
Response will be based on review of scans by centralized radiological review
committee.
* Objective response rate in all subjects receiving INCB054828 administered as
continuous dose regimen or intermittent dose regimen (Cohorts A-ID, A-CD, and B
combined). Response will be based on review of scans by a centralized
radiological review committee.
* Objective response rate in subjects with all other FGF/FGFR alterations
(Cohort B). Response will be based on review of scans by a centralized
radiological review committee.
* Progression-free survival (Cohort A-ID, Cohort A-CD, and Cohort B,
separately).
* Duration of response (Cohort A-ID, Cohort A-CD, and Cohort B, separately).
* Overall survival (Cohort A-ID, Cohort A-CD, and Cohort B, separately).
* Safety and tolerability, assessed by monitoring the frequency, duration, and
severity of adverse events (AEs); through physical examinations; by evaluating
changes in vital signs and electrocardiograms (ECGs); and through clinical
laboratory blood and urine sample evaluations.
Background summary
INCB054828 is an inhibitor of the fibroblast growth factor receptor (FGFR)
family of receptor tyrosine kinases that is proposed for the treatment of
advanced malignancies. Aberrant signaling through FGFR resulting from gene
amplification or mutation, chromosomal translocation, and ligand-dependent
activation of the receptors has been demonstrated in multiple types of human
cancers, including urothelial cancers. Fibroblast growth factor receptor
signaling contributes to the development of malignancies by promoting tumor
cell proliferation, survival, migration, and angiogenesis. Incyte is proposing
to study INCB054828 for the treatment of advanced/nonresectable or metastatic
urothelial carcinoma with fibroblast growth factor (FGF)/FGFR genetic
alterations.
Study objective
The primary objective of this study is to evaluate the objective response rate
(ORR) of INCB054828 as a monotherapy in the treatment of metastatic or
surgically unresectable urothelial carcinoma harboring FGF/FGFR 3 mutations or
fusions.
The secondary objectives of this study are to
- To evaluate the efficacy of INCB054828 in subjects with advanced/metastatic
or surgically unresectable urothelial cancer with
different molecular subgroups.
- evaluate the safety and tolerability of INCB054828 and
- evaluate other clinical efficacy measurements, including duration of response
(DOR), progression free survival (PFS), and overall survival (OS).
An exploratory objective of this study is to obtain additional data on
predictive biomarkers to identify subgroups that would benefit most from
INCB054828 in the presence of FGF/FGFR alterations.
Study design
This is an open-label monotherapy study of INCB054828. Subjects will be
enrolled into 1 of 3 cohorts. A subject*s cohort will be determined by FGF/FGFR
gene alteration status.
* Cohort A-ID: FGFR3 mutations or fusions (n = 100); this cohort will complete
enrollment before Cohort A-CD begins enrolling subjects.
* Cohort A-CD: FGFR3 mutations or fusions (n = 100)
* Cohort B: all other FGF/FGFR alterations (40 subjects)
Intervention
INCB054828 will be self-administered as a QD oral treatment on a 21-day cycle.
Subjects will take study drug for 2 weeks continuously (14 days) followed by a
1-week (7 days) break. The starting dose will be 13.5 mg. Each dose of study
drug should be taken immediately upon rising or after a 2-hour fast. Subjects
should plan to fast for 1 additional hour after taking study drug.
Study burden and risks
Based on an expected average participation of approximately 6 months, the study
entails around 16 visits including physical examinations (i.e. eye exam, vital
signs, weight assessment),14 venapunctions, 4 CT-scans and 13 ECGs.
Patients have to take study drug immediately after waking up or 2 hours before
eating and not eat for 1 hour after taking study drug, and follow a diet.
Subjects will be tested on hepatitis B and C and pregnancy.
Patient or partner should not get pregnant during the study.
Patient should protect him/herself from sunlight.
There is a risk of the following side effects:
* * Hyperphosphatemia - an increase in phosphate levels in the blood and the
kidney's inability to get rid of the increased levels of phosphate (a component
of bone and other tissues). Please report any symptoms of hyperphosphatemia
such as muscle cramps, twitching, or mouth numbness or tingling
* Fatigue (feeling tired)
* Dry mouth
* Alopecia (hair loss and/or thinning)
* Diarrhea (loose, watery bowel movement)
* Stomatitis (redness and sores in your mouth and/or throat)
* Anemia (low hemoglobin levels in blood)
* Dehydration (not enough water in your body)
* Decreased appetite
* Dysgeusia (sense of taste is off)
* Blurred vision
* Weight decreased
* Constipation (cannot have or difficulty having bowel movement)
* Cough
* Epistaxis (nose bleeds)
* Nausea
* Pain in extremity
* Abdominal pain
* Aspartate aminotransferase increased (increase in a type of liver enzyme)
* Back pain
* Dry eye
* Dyspnea (shortness of breath)
* Hyponatremia (low sodium levels in the blood)
* Hypophosphatemia (low phosphate level in the blood)
* Musculoskeletal pain
* Pneumonia
* Vomiting
* Alanine aminotransferase increased (increase in a type of liver enzymes)
* Ascites (accumulation of fluid between the lining of the abdomen and organs)
* Dyspepsia (impaired digestion)
* Hypercalcemia (high calcium level in the blood)
* Hypoesthesia (reduced sense of touch)
* Hypoalbuminemia (low albumin levels in blood)
* Hypokalemia (low potassium in blood)
* Pain
* Paronychia (infection of the nails)
* Upper respiratory tract infection
* Vitamin D deficiency
* Wheezing
For further information on potential risks see section 1.3 of the protocol.
There is no guarantee that patients will receive personal benefit from taking
part in this study. However, by taking part in this study, patients may
benefit if the treatment turns out to be effective. Furthermore, patients will
have close medical monitoring of their health condition by blood tests and
other tests during clinic visits.
Patients may be withdrawn from participation if FGF/FGFR alteration is not
confirmed by the central lab and the patient does not benefit from treatment.
Augustine Cut-Off 1801
Wilmington DE 19803
US
Augustine Cut-Off 1801
Wilmington DE 19803
US
Listed location countries
Age
Inclusion criteria
* Men and women, aged 18 or older. For subjects in Japan, if the subject is
below the age of 20 years, voluntary agreement shall be obtained from the
subject and the representative or legal guardian using the written consent
form., * Histologically documented metastatic or surgically unresectable
urothelial carcinoma; may include primary site from urethra, ureters, upper
tract, renal pelvis, and bladder., * Eastern Cooperative Oncology Group (ECOG)
performance status of 0, 1, or 2.
* Life expectancy * 12 weeks. , * Radiographically measurable disease per
RECIST v1.1., * Documented FGF/FGFR alteration and have either:
* have failed at least 1 previous treatment for their metastatic or surgically
unresectable urothelial carcinoma (ie, chemotherapy, immunotherapy), or
* have not received chemotherapy for metastatic or surgically unresectable
urothelial carcinoma due to poor performance status (ie,
ECOG performance status of 2) and insufficient renal function (ie, creatinine
clearance < 60 mL/min or local guidelines)., * Willingness to avoid pregnancy
or fathering children. For subjects in Japan, female subjects who have been
amenorrhoeic for at least 12 months resulting from chemotherapy/radiotherapy
are considered of childbearing potential and should agree to use adequate
contraceptive measures.
Exclusion criteria
* Treatment with other investigational study drug for any indication for any
reason, or receipt of anticancer medications within 28 days before first dose
of study drug. Subjects must have recovered (Grade * 1 or at pretreatment
baseline) from AEs from previously administered therapies.
* Prior receipt of a selective FGFR inhibitor.
* Abnormal laboratory parameters:
* Total bilirubin * 1.5 × upper limit of normal (ULN; * 2.5 × ULN if Gilbert
syndrome or metastatic disease involving liver).
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 ×
ULN (AST and ALT > 5 × ULN in the presence of liver
metastases).
* Creatinine clearance * 30 mL/min based on Cockroft-Gault.
* Serum phosphate > institutional ULN.
* Serum calcium outside of the institutional normal range or serum
albumin-corrected calcium outside of the institutional normal range when serum
albumin is outside of the institutional normal range., * Use of any potent
CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is
shorter) before the first dose of study drug., * Known hypersensitivity or
severe reaction to INCB054828 or excipients of INCB054828 study drug., *
Inability or unwillingness to swallow INCB054828 or significant
gastrointestinal disorder(s) that could interfere with the absorption,
metabolism, or excretion of INCB054828., * Subjects who require hemodialysis.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-001321-14-NL |
| ClinicalTrials.gov | NCT02872714 |
| CCMO | NL59441.100.16 |