FGFR-positive locally advanced or metastatic urothelial carcinoma MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864
Conditions
Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A: • Male/female patients = 18 years of age (at least age of legal maturity) • Urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria: o Histologically confirmed. o Patients with mixed histology are required to have a dominant transitional cell pattern o Locally advanced (T4, any N; or any T, N2-3) or metastatic disease (any T, any N and M1) Note: 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) • 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 • Measurable disease according to RECIST v1.1 • ECOG PS 0 or 1 • Adequate hematological and end organ function • Recovery to NCI CTCAE v.4.03 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug / procedure-related toxicity (patients with persistent alopecia, anemia [hemoglobin = 9 g/dl], and / or hypothyroidism can be included) • No prior systemic treatment for locally advanced or metastatic urothelial carcinoma. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. Prior local intra-vesical chemotherapy/local immunotherapy allowed if completed at least 4 weeks before first study drug administration • Ineligibility for cisplatin-based chemotherapy • Negative serum pregnancy test in women of childbearing potential (performed within 7 days before the first treatment). Negative results must be available before the first study drug administration • WOCBP + fertile men must agree to use adequate contraception when sexually active from signing of ICF for study treatment eligibility until at least 5 months after last study drug administration. Investigator or designated associate is requested to advise patient how to achieve highly effective birth control. Highly effective (failure rate of less than 1% per year) contraception methods include: • Combined (estrogen and progesterone containing: oral, intravaginal, transdermal) and progesterone-only (oral, injectable, implantable) hormonal contraception associated with inhibition of ovulation • IUD/IUS • Bilateral tubal occlusion/vasectomized partner • Sexual abstinence o Periodic abstinence + withdrawal are not acceptable methods of contraception. Male patients with female partner of childbearing potential must use condom+ ensure that an additional form of contraception is also used during treatment + until 12 weeks after last study drug administration Part B: • Male/female patients = 18 years of age (at least age of legal maturity) • Urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria: o Histologically confirmed o Patients with mixed histology are required to have a dominant transitional cell pattern. o Locally advanced (T4, any N; or any T, N2-3) or metastatic disease (any T, any N, and M1) Note: Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (
Exclusion criteria
Exclusion criteria: Part A: • Inability to swallow oral medications • Any malabsorption condition • Current diagnosis of retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion • Previous or concurrent cancer except o cervical carcinoma in situ o treated basal-cell carcinoma or squamous cell skin cancer o localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score = 6 and PSA 3 years before the first study drug administration • Investigational drug treatment outside of this study during or within 4 weeks before the first study drug administration • Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies) • Previous assignment to treatment during this study • Severe (CTCAE v.4.03 Grade 3) infections within 4 weeks before the first study drug administration, including but not limited to hospitalization for complication of infection, bacteremia, or severe pneumonia • History of autoimmune disease except: a) autoimmune-related hypothyroidism clinically stable on thyroid replacement hormone; b) controlled Type-I diabetes mellitus on a stable dose of insulin regimen • History or current condition of uncontrolled cardiovascular disease • Systolic/diastolic blood pressure = 100/60 mmHg and heart rate = 100/min • Renal failure requiring peritoneal dialysis or hemodialysis • Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia) • Concomitant therapies that are known to increase serum calcium or phosphate levels and that cannot be discontinued or switched to a different medication before start of study treatment • Evidence or history of bleeding diathesis or coagulopathy • Any hemorrhage / bleeding event CTCAE v.4.03 = Grade 3 within 4 weeks before the first study drug administration Part B: • Inability to swallow oral medications • Any malabsorption condition • Current diagnosis of retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion • Previous or concurrent cancer except o cervical carcinoma in situ o treated basal-cell carcinoma or squamous cell skin cancer o localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score = 6, and PSA = 10 ng/mL undergoing active surveillance and treatment-naïve o any other cancer curatively treated > 3 years before randomization • Ongoing or previous anti-cancer treatment within 4 weeks before randomization • Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies) • Previous assignment to treatment during this study • Severe (CTCAE v.4.03 Grade 3) infections within 4 weeks before randomization, including but not limited to hospitalization for complication of infection, bacteremia, or severe pneumonia • History of autoimmune disease except: a) autoimmune-related hypothyroidism clinically
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: • To determine the safety and tolerability of rogaratinib in combination with atezolizumab in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma • To determine the recommended Phase 2 dose (RP2D) of rogaratinib in combination with atezolizumab in this patient population. Part B: • To compare progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR positive locally advanced or metastatic urothelial carcinoma. ;Secondary Objective: Part A: • To assess the efficacy of the combination of rogaratinib and atezolizumab in this patient population. • To characterize the pharmacokinetics (PK) of rogaratinib in combination with atezolizumab in this patient population Part B: • To further characterize the pharmacokinetics of rogaratinib in combination with atezolizumab in this patient population • To further assess the efficacy of the combination of rogaratinib and atezolizumab in this patient population • To evaluate the safety and tolerability of rogaratinib in combination with atezolizumab in this patient population;Primary end point(s): Part A: • The incidence of DLTs used to determine the MTD and/or RP2D • The incidence of treatment-emergent adverse events (TEAEs) • The incidence of treatment-emergent drug-related TEAEs • The incidence of treatment-emergent serious adverse events Part B: • Treatment efficacy as assessed by progression-free survival, as assessed by RECIST 1.1;Timepoint(s) of evaluation of this end point: Part A: • Safety - throughout the study • MTD – up to 21 days Part B: • RECIST - every 9 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: • Treatment efficacy as assessed by Objective response rate (ORR), as assessed by RECIST 1.1 • Cmax of rogaratinib • AUC(0-8) of rogaratinib Part B: • The incidence of treatment-emergent adverse events (TEAEs) • The incidence of treatment-emergent drug-related TEAEs • The incidence of treatment-emergent serious adverse events • Change in vital signs, physical finding and clinical laboratory results • Treatment efficacy as assessed by Disease control rate (DCR), as assessed by RECIST 1.1 • Treatment efficacy as assessed by Duration of response (DOR), as assessed by RECIST 1.1 • Treatment efficacy as assessed by Objective response rate (ORR), as assessed by RECIST 1.1 • Treatment efficacy as assessed by Overall survival (OS), as assessed by RECIST 1.1 • Rogaratinib and Atezolizumab pharmacokinetic concentration data ;Timepoint(s) of evaluation of this end point: Part A: • RECIST - every 9 weeks • PK – up to C5D1 Part B: • Safety - throughout the study • PK – up to C5D1 | — |
Countries
Austria, France, Germany, Italy, Japan, Korea, Republic of, Spain, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer AG
Outcome results
None listed