Phase 2/3 study of rogaratinib (pan FGFR inhibitor) vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma with a high amount of specific cell growth factor receptors 1 and 3 (FGFR1 and 3) in the tumor cells
- Conditions
- mRNA FGF receptor 1 and 3 positive locally advanced or metastatic urothelial carcinoma progressed after prior platinum-containing chemotherapyMedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004340-11-IT
- Lead Sponsor
- BAYER HEALTHCARE AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 1627
Existence of archival or fresh biopsy for FGFR testing.
FGFR testing of patients will be performed at the investigators' discretion up to a max. of 90 days prior to start of screening (signing of informed consent for study treatment eligibility). Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment within this timeframe. If the patient is positive for FGFR 1
and/or 3 and is unable start screening by 90 days after FGFR testing, the patient may still be considered for screening after discussion with the
sponsor's designated medical representative and approval by the sponsor
Male or female patients = 18 years of age (at least age of legal
maturity).
Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:
Histologically or cytologically confirmed. Patients with mixed histologies are required to have a dominant transitional cell pattern.
Locally advanced (T4b, any N; or any T, N 2-3) or metastatic disease (any T, any N and M1).
Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal
disease (N2-3).
ECOG Performance Status of 0 or 1.
Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at
least 2 cycles). In patients who received prior adjuvant/neoadjuvant platinum-containing chemotherapy, progression had to occur within 12
months of treatment.
High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh tumor biopsy
specimen.
At least 1 measurable lesion according to Response Evaluation Criteria in
Solid Tumors (RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI.
Adequate laboratory and organ function:
Absolute neutrophil count (ANC) = 1,500/mm3
Platelet count = 100,000/mm3
Hemoglobin = 9.0 g/dL (without transfusion or erythropoietin within 4
weeks before randomization).
Total bilirubin = 1.5 times the upper limit of normal (ULN). Known
Gilbert syndrome is allowed if total bilirubin is = 3 x ULN.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =
2.5 x ULN (= 5 x ULN for patients with liver involvement of their cancer).
Alkaline phosphatase limit = 2.5 x ULN (= 5 x ULN for patients with liver
and bone involvement of their cancer).
Lipase < 2 x ULN
Glomerular filtration rate (GFR) = 30 mL/min/1.73 m2 according to
Modification of Diet in Renal Disease (MDRD) abbreviated formula.
International normalized ratio (INR) = 1.5 ? ULN, and partial
thromboplastin time (PTT) or activated PTT (aPTT) = 1.5 ? ULN. Patients
being treated with anticoagulant, e.g. warfarin or heparin, will be
allowed to participate provided no prior evidence of an underlying
Previous or concurrent cancer except:
cervical carcinoma in situ
treated basal-cell or squamous cell skin carcinoma
any cancer curatively treated > 3 years before randomization
ocuratively treated incidental prostate cancer (T1/T2a)
Symptomatic metastatic brain or meningeal tumors unless the patient is
> 6 months from definitive therapy, has no radiological evidence of tumor growth and is clinically stable with respect to the tumor at
randomization. Also the patient must not be undergoing acute steroid
therapy or taper (chronic steroid therapy is acceptable provided that the
dose is stable for one month prior to and following screening
radiographic studies).
Known human immunodeficiency virus (HIV) infection.
Renal dialysis.
Any malabsorption condition.
Breast-feeding.
Ongoing or previous treatment with anti-FGFR directed therapies (e.g.
receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific
antibodies) or with taxanes or vinflunine.
More than two prior lines of systemic anti-cancer therapy for urothelial
carcinoma.
Ongoing or previous anti-cancer treatment within 4 weeks before
randomization:
Patients who have received prior treatment with anti-CTLA-4 may be
enrolled provided at least 5 half-lives (approximately 75 days) have
elapsed before randomization.
Prior cancer vaccines and cellular immunotherapy are permitted.
Previous radiotherapy is acceptable under the following conditions:
Therapeutic radiotherapy = 3 weeks before the baseline tumor scan.
Palliative radiotherapy for bone metastases or soft tissue lesions is
allowed and should be completed >7 days prior to baseline tumor scan.
Lesions at the site of previous radiotherapy should have evidence of
progressive disease if this is the only site of disease.
Anti-cancer therapy is defined as any agent or combination of agents
with clinically proven anti-tumor activity administered by any route with
the purpose of affecting the malignancy, either directly or indirectly,
including palliative and therapeutic endpoints.
Use of strong inhibitors and inducers of CYP3A4 (see Appendix 16.1)
should have been stopped 2 weeks before randomization.
Concomitant therapies that are known to increase serum calcium or
phosphate levels and cannot be discontinued or switched to a different
medication before randomization.
Substance abuse, medical, psychological or social conditions that may
interfere with the patient's participation in the study or evaluation of the
study results.
Major surgery, or significant trauma within 4 weeks before
randomization (central line surgery is not considered major surgery).
Unresolved toxicity higher than National Cancer Institute's Common
Terminology Criteria for Adverse Events, version 4.03 (
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