Clinical trial NCT03788603: Rogaratinib (BAY1163877) in Chinese Patients
Official title: An Open Label, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Rogaratinib (BAY1163877) in Chinese Patients With FGFR-positive Refractory, Locally Advanced, or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-12-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is planned to determine the safety and tolerability of rogaratinib in Chinese patients with fibroblast growth factor receptor (FGFR)-positive refractory, locally advanced, or metastatic solid tumors and to characterize the pharmacokinetics of rogaratinib in Chinese patients.


Eligibility criteria: Inclusion Criteria:

* Male or female patients ≥18 years of age on the date of signing the Main Informed Consent Form.
* Subjects with histologically or cytologically confirmed, refractory, locally advanced, or metastatic solid tumors who are not candidates for any standard therapy, excluding primary brain or spinal tumors.
* High FGFR1, 2, 3 or 4 mRNA expression levels based on archival or fresh tumor biopsy specimen analysis (RNAscope score of 3 or 4)
* At least one measurable lesion outside the central nervous system according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) A lesion in a previously irradiated area is eligible and to be considered measurable disease as long as there is objective evidence of progression of the lesion prior to study enrollment. Patients with resected primary tumors who have documented metastases are eligible.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
* Life expectancy of at least 3 months
* Adequate bone marrow, liver and renal function as assessed by laboratory requirements conducted within 7 days before the first dose of rogaratinib:

  * Hemoglobin (Hb) ≥9.0 g/dL (without transfusion or erythropoietin within 4 weeks before screening)
  * Absolute neutrophil count (ANC) ≥1,500/mm3
  * Platelet count ≥100,000/mm3
  * Total bilirubin ≤1.5 times the upper limit of normal (ULN). Documented or diagnosed constitutional jaundice such as Gilbert syndrome is allowed if total bilirubin is mildly elevated (\<6 mg/dL).
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN (≤5 times ULN for patients with liver involvement of their cancer)
  * Alkaline phosphatase ≤2.5 times ULN (≤5 times ULN for patients with liver involvement of their cancer)
  * Amylase and lipase ≤2.5 times ULN
  * Serum creatinine ≤1.5 x ULN and glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2, according to the Modified Diet in Renal Disease (MDRD) abbreviated formula

Exclusion Criteria:

- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study.

The following previous or concurrent cancer types might be acceptable: cervical carcinoma in situ, treated basal cell carcinoma, locally confined prostate cancer, or any cancer curatively treated \>3 years before the start of rogaratinib.

- Symptomatic brain or meningeal or spinal metastases.

Asymptomatic brain or meningeal or spinal metastases are acceptable if all of the following criteria are met:

* Definitive therapy completed \>6 months before the start of rogaratinib
* No evidence of the growth of brain or meningeal or spinal metastases on an imaging test performed within 4 weeks before the start of rogaratinib
* Clinically and radiologically stable with respect to the tumor at the time of study entry

  * Moderate or severe liver cirrhosis (Child-Pugh class B or C)
  * History or current evidence of altered endocrine regulation of calcium phosphate homeostasis (e.g. parathyroidectomy, parathyroid disorder, tumor lysis, tumoral calcinosis)
  * Any previous drug / procedure-related toxicity (patients with persistent alopecia, anemia, and / or hypothyroidism can be included) not recovered to National Cancer Institute's Common Terminology Criteria for Adverse Event, version 4.03 (CTCAE v4.03) Grade 0 or 1 or not recovered to baseline preceding the prior treatment
  * Current diagnosis of any retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.
  * Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies)

Primary outcomes:
measure: Frequency of Treatment-Emergent Adverse Events(TEAEs)
timeFrame: 30 days after last dose of rogaratinib
measure: Severity of Treatment-Emergent Adverse Events(TEAEs)
timeFrame: 30 days after last dose of rogaratinib
measure: Cmax: Maximum drug concentration in plasma after dose administration
timeFrame: Cycle 1 Day 1 (each cycle is 21 days)
measure: AUC(0-12): AUC from time zero to 12 hours p.a. after first-dose administration
timeFrame: Cycle 1 Day 1 (each cycle is 21 days)
measure: Cmax,md: Cmax after multiple dosing
timeFrame: Cycle 1 Day 15 (each cycle is 21 days)
measure: AUC(0-12)md: AUC(0-12) after multiple dosing
timeFrame: Cycle 1 Day 15 (each cycle is 21 days)
Secondary outcomes:
measure: Phosphate levels
timeFrame: Within 7-14 days after the last dose of rogaratinib
measure: Response rate
timeFrame: Within 7-14 days after the last dose of rogaratinib
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
Study officials:
References: