Phase 1b/2 study of rogaratinib (BAY 1163877) in combination with atezolizumab in urothelial carcinoma
- Conditions
- FGFR-positive locally advanced or metastatic urothelial carcinomaMedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001483-38-FR
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 190
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 (
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 < 10 ng/mL undergoing active surveillance and treatment-naïve)
o any other cancer curatively treated > 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
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