A study to evaluate Infigratinib in patients with Urothelial Carcinoma
- Conditions
- Invasive Urothelial Carcinoma with Susceptible FGFR3 Genetic AlterationsMedDRA version: 21.0Level: LLTClassification code 10046731Term: Urothelial carcinoma urethra recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003248-63-ES
- Lead Sponsor
- QED Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 218
To be eligible for the study, a subject must meet all of the following criteria:
1. Are =18 years of age (=20 years of age in Taiwan) of either sex.
2. Have signed informed consent.
3. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations within 120 days following nephroureterectomy, distal ureterectomy, or cystectomy:
• Regarding samples and documentation of FGFR3 alterations (see also Section 10.3):
? FGFR3 mutation is confirmed if: FGFR3 gene is mutated in Exon 7 (R248C, S249C), Exon 10 (G370C, A391E, Y373C), or Exon 15 (K650M/T, K650E/Q).
? FGFR3 gene fusion or translocation is confirmed if: gene fusion or translocation is identified.
? The amino acid numbers for the FGFR3 mutations refer to the functional FGFR3 isoform 1 (NP_000133.1) that is the NCBI Refseq ID used to report genetic alterations in FGFR3 by the FoundationOne CDx test.
? Written documentation of central laboratory determination by FoundationOne CDx testing (through Foundation Medicine USA) of FGFR3 alterations is required for study eligibility in study centers outside of China. For study centers in China, confirmation is needed by a test equivalent to that of the central test.
? For patients who require molecular prescreening to confirm the presence of the FGFR3 alteration to meet the inclusion criteria, an archival tumor sample with a pathology report must be sent to Foundation Medicine USA for FoundationOne CDx testing.
? For study sites in China, written documentation of FGFR3 alterations by the contracted central laboratory is required for study eligibility.
• If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be AJCC Stage = ypT2 and/or yN+. Prior neoadjuvant therapy is defined as at least 3 cycles of neoadjuvant cisplatin-based chemotherapy with a planned cisplatin dose of 70 mg/m2/cycle. Patients who received less than this or non-cisplatin-based neoadjuvant treatment will be considered as having received no neoadjuvant chemotherapy.
• If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky et al (2011):
Creatinine clearance =60 mL/minute, or
Common Terminology Criteria for Adverse Events (CTCAE version 5.0 or later) Grade =2 hearing loss, or
? CTCAE Grade =2 neuropathy.
• If cisplatin ineligible based on Galsky et al (2011), must also meet the following criteria:
? Upper tract disease should be AJCC Stage =pT2 pN0-2 M0 (post-lymphadenectomy or no lymphadenectomy [pNx]).
? UBC should be AJCC Stage =pT3 or pN+.
• Must have a centrally reviewed negative postoperative CT (defined as lymph nodes with short axis <1.0 cm and without growth and no distant metastases according to Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) or negative biopsy within 28 days before randomization to confirm absence of disease at baseline.
4. If have had AEs associated with prior surgery or neoadjuvant chemotherapy, they have stabilized or resolved to Grade =2 before randomization.
5. Have Eastern Cooperative Oncology Group (ECOG) performance status of =2.
6. If a woman of childbearing potential (WOCBP), must have a negative pregnancy test within 7 days of the first dose of study drug. A woman is not of childbearing potential if she has undergone surgical sterilization (total hysterectomy, or bilateral tubal ligation, or bilateral oophorectomy =6 weeks before taking study drug) or if she is postmenopausal and
To be eligible for the study, a subject must not meet any of the following criteria:
1. Presence of positive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy.
2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for NMIBC within the previous 30 days.
3. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone. See Appendix 2 (Section 17.2).
• Prior neoadjuvant chemotherapy or immunotherapy is allowed if inclusion criterion #3 is met. Prior chemotherapy must have been completed within a period of time that is greater than the cycle length used for that treatment before first dose of study drug. Subjects who received biologic therapy should have completed therapy with a period that is =5 half-lives before the first dose of study drug.
4. Are planning to receive other systemic therapies intended to treat invasive urothelial carcinoma while on this study.
5. Have previously or currently is receiving treatment with a MEK or selective FGFR inhibitor.
6. Have a history of primary malignancy within the past 3 years other than (1) invasive UBC or UTUC (ie, disease under study), (2) noninvasive urothelial carcinoma, (3) any adequately treated in situ carcinoma or non-melanoma carcinoma of the skin, (4) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (5) an untreated cancer on surveillance that may not affect the subject’s survival status for =3 years based on clinician assessment/statement. For any other cancers that do not meet the criteria above, written approval is required by the Medical Monitor.
7. Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the Investigator to pose minimal risk for study participation may be enrolled in the study.
8. Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, vasculature, myocardium, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, small renal cyst or stone calcifications, and asymptomatic coronary calcification.
9. Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg, active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
10. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
11. Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, or Seville oranges or products containing juice of these fruits within 7 days before the first dose of study drug.
12. Have used medications that are known to prolong the QT interval and/or are associated with a risk of Torsades de
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method