Status:

TERMINATED

Safety and Efficacy of Pemigatinib in Patients With High-risk Urothelial Cancer After Radical Surgery

Lead Sponsor:

European Association of Urology Research Foundation

Collaborating Sponsors:

Incyte Biosciences International Sàrl

AMS Advanced Medical Services GmbH

Conditions:

Urothelial Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

The purpose of this clinical trial is to demonstrate the benefit of Pemigatinib, a drug that has indicated promising effects for relapse free survival in molecularly-selected, high-risk patients with ...

Detailed Description

This is an open-label, single-arm, Phase II study, evaluating safety and efficacy of INCB054828 (Pemigatinib) as adjuvant therapy for molecularly-selected, high-risk patients with urothelial carcinoma...

Eligibility Criteria

Inclusion

  • Histological evidence of pT3-4 and/or pN1-3 UC of the urinary bladder or upper urinary tract after radical cystectomy / radical nephroureterectomy. Patients with mixed histologies are required to have a dominant (i.e. at least 50%) urothelial cell carcinoma pattern.
  • Previous administration of at least 3 cycles of neoadjuvant cisplatin-based chemotherapy OR, if neoadjuvant chemotherapy was not administered, ineligibility to receive cisplatin-based adjuvant chemotherapy based on Galsky's criteria, that include at least one of the following: (1) WHO performance status ≥ 2 and/or (2) creatinine-clearance \< 60 ml/min and/or (3) CTCAE Gr ≥ 2 hearing loss and/or (4) CTCAE Gr ≥ 2 neuropathy.
  • Evidence of FGFR alterations (mutations or translocations as specified in protocol) as assessed by a centralized Foundation Medicine test (Foundation One).
  • Recovered with no evidence of disease confirmed by radiological images, prior to start of adjuvant therapy within 13 weeks after radical surgery.
  • Willingness to avoid pregnancy or fathering children
  • Written informed consent.

Exclusion

  • Any previous receipt of a selective FGFR inhibitor.
  • Presence of primary CIS only.
  • Presence of another malignancy in the 3 years before enrolment except for basal cell carcinoma or squamous cell carcinoma of the skin, cis of cervix, localised prostate cancer in active surveillance or other non invasive or other indolent malignancy that has undergone potentially curative therapy.
  • Presence of pregnancy or lactation.
  • Distant metastases (M1 disease).
  • Treatment with other investigational drugs, receipt of anticancer medications (except for neoadjuvant cisplatin-based chemotherapy, see second inclusion criterion) or radiotherapy after radical surgery.
  • Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment.
  • Abnormal laboratory parameters:
  • Total bilirubin ≥ 1.5 × upper limit of normal (ULN; ≥ 2.5 × ULN if Gilbert syndrome).
  • AST and/or ALT \> 2.5 × ULN
  • 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.
  • History of human immunodeficiency virus infection or active tuberculosis infection.
  • Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (exceeding \> 10 mg daily of prednison equivalent; inhalation steroids are permitted).
  • Evidence of hepatitis B virus or hepatitis C virus active infection or risk of reactivation.
  • Severe hepatic impairment
  • Known prior severe hypersensitivity to investigational products or its excipients
  • History of clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of enrolment, New York Heart Association Class III or IV.
  • Current evidence of corneal disorder/keratopathy (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc) or retinal disorder (including but not limited to, central serous retinopathy, macular/retinal degeneration, diabetic retino-pathy, retinal detachment, etc) as confirmed by ophthalmologic examination.
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits.

Key Trial Info

Start Date :

July 13 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

November 15 2022

Estimated Enrollment :

2 Patients enrolled

Trial Details

Trial ID

NCT04294277

Start Date

July 13 2020

End Date

November 15 2022

Last Update

April 18 2025

Active Locations (5)

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Page 1 of 2 (5 locations)

1

ASST Papa Giovanni XXIII

Bergamo, Italy

2

Policlinico Sant'Orsola-Malpighi - Azienda Ospedaliero-Univeristaria di Bologna

Bologna, Italy

3

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

4

IRCCS San Raffaele Hospital

Milan, Italy