check_circleStudy Completed

Advanced or metastatic solid tumor

Phase 1 study of the combination of rogaratinib with copanlisib in patients with Fibroblast growth factor receptor (FGFR)-positive, locally advanced or metastatic solid tumors

Trial purpose

The primary objective of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) and efficacy of rogaratinib in combination with copanlisib in patients with locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

The secondary objectives of this study are to characterize the pharmacokinetics (PK) of rogaratinib and copanlisib alone and in combination, and to assess the anti-tumor efficacy of rogaratinib in combination with copanlisib for locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - High FGFR mRNA expression levels (RNAscope score of ≥3; measurement is part of this protocol) in archival or fresh tumor biopsy specimen.
    - Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
    - At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in contrast enhanced (unless contraindicated) CT or MRI.
    - Adequate bone marrow, liver and renal function.
    - Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m*2 according to the Modification of Diet in Renal Disease (MDRD) formula.
    - Left ventricular ejection fraction (LVEF) equal to or above the lower limit of normal (LLN) at the institution.
    - Life expectancy of at least 3 months.
    - For the dose escalation part: Patients with histologically confirmed, locally advanced or metastatic solid tumors who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anti-cancer treatment is no longer effective, excluding primary brain or spinal tumors. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.
    - For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.
  • - Previous or concurrent cancer that is distinct from tumor for which the patient is enrolled in the study, except
     -- curatively treated cervical carcinoma in situ
     -- treated basal-cell carcinoma
     -- localized prostate cancer treated with curative intent and known 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)
     -- any cancer curatively treated > 3 years before planned start of study treatment.
    - Ongoing or previous anti-cancer treatment within 4 weeks of study treatment start (or 6 weeks for mitomycin C, nitrosoureas and monoclonal antibodies); with exceptions.
    - Prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation (previous exposure is allowed in other circumstances). If prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation is different from the known safety profile of rogaratinib or copanlisib, enrollment is allowed.
    - Symptomatic brain or meningeal metastatic tumors unless the patient is >6 months from definitive therapy, has no evidence of tumor growth on an imaging study and is clinically stable with respect to the tumor at the start of study treatment. 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).
    - History or current condition of an uncontrolled cardiovascular disease including congestive heart failure NYHA > Class 2, unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months) or myocardial infarction within past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
    - Active hepatitis B (HBV) or C (HCV) infection.
    - Active clinically serious infections (≥ CTCAE v4.03 Grade 2).

Trial summary

Enrollment Goal
16
Trial Dates
July 2018 - February 2021
Phase
Phase 1
Could I Receive a placebo
No
Products
Rogaratinib (BAY1163877)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Universitätsklinikum KölnKöln, 50937, Germany
Completed
Klinikum der Universität WürzburgWürzburg, 97080, Germany
Completed
Krankenhaus NordwestFrankfurt, 60488, Germany
Withdrawn
Universitätsklinikum Hamburg Eppendorf (UKE)Hamburg, 20246, Germany
Completed
Memorial Sloan-Kettering Cancer CenterNew York, 10065, United States
Completed
Dana-Farber Cancer InstituteBoston, 02215, United States
Completed
Barbara Ann Karmanos Cancer Institute - DetroitDetroit, 48201, United States
Completed
Northwestern UniversityChicago, 60611, United States
Completed
CU Saint-Luc/UZ St-LucBRUXELLES - BRUSSEL, 1200, Belgium
Completed
CHU de LiègeLIEGE, 4000, Belgium
Completed
UZ AntwerpenEDEGEM, 2650, Belgium
Completed
Samsung Medical CenterSeoul, 06351, Korea, Republic Of
Withdrawn
Centre Oscar Lambret - LilleLILLE cedex, 59020, France
Withdrawn
Centre Léon BérardLYON CEDEX, 69008, France
Completed
Severance Hospital, Yonsei University Health SystemSeoul, 03722, Korea, Republic Of
Completed
Asan Medical CenterSeoul, 05505, Korea, Republic Of
Completed
National University HospitalSingapore, 119074, Singapore
Completed
National Cancer Center SingaporeSingapore, 169610, Singapore
Completed
Ciutat Sanitària i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Withdrawn
Hospital Clínic i Provincial de BarcelonaBarcelona, 08036, Spain
Withdrawn
Hospital General Universitario Gregorio MarañónMadrid, 28007, Spain
Completed
Hospital Clínico Universitario de ValenciaValencia, 46010, Spain
Withdrawn
MD Anderson International Espanya, S.A.Madrid, 28033, Spain
Completed
USC Norris Hospital and ClinicsLos Angeles, 90033, United States
Completed
University of MarylandBaltimore, 21201, United States
Withdrawn
Prisma HealthGreenville, 29605, United States
Completed
Tyler Cancer CenterTyler, 75702, United States
Withdrawn
Texas Oncology- Austin MidtownAustin, 78705, United States
Withdrawn
Comprehensive Cancer Centers of NevadaLas Vegas, 89169, United States

Primary Outcome

  • Incidence of treatment-emergent adverse events (TEAEs)
    date_rangeTime Frame:
    Up to 32 months
  • Incidence of drug-related TEAEs
    date_rangeTime Frame:
    Up to 32 months
  • Incidence of treatment-emergent serious adverse events (TESAEs)
    date_rangeTime Frame:
    Up to 32 months
  • Incidence of Dose-limiting toxicities (DLTs)
    date_rangeTime Frame:
    Approximately 10 months
  • Objective response rate (ORR) at recommended dose
    ORR in patients receiving the recommended dose of the rogaratinib-copanlisib-combination during the dose expansion part
    date_rangeTime Frame:
    Up to 32 months

Secondary Outcome

  • Maximum plasma concentration of Copanlisib (Cmax)
    date_rangeTime Frame:
    0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Area under the plasma concentration versus time curve of Copanlisib (AUC (0-48))
    date_rangeTime Frame:
    0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Area under the plasma concentration versus time curve of Rogaratinib (AUC (0-8))
    date_rangeTime Frame:
    0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Maximum plasma concentration of Rogaratinib (Cmax)
    date_rangeTime Frame:
    0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Objective response rate (ORR)
    date_rangeTime Frame:
    Up to 32 months
  • Disease control rate (DCR)
    date_rangeTime Frame:
    Up to 32 months
  • Duration of response (DOR) for Partial Response and Complete Response
    date_rangeTime Frame:
    Up to 32 months
  • Progression-free survival (PFS)
    date_rangeTime Frame:
    Up to 32 months
  • Overall survival (OS)
    date_rangeTime Frame:
    Up to 32 months

Trial design

A multicenter Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of the combination of rogaratinib and copanlisib in patients with FGFR-positive, locally advanced or metastatic solid tumors
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
N/A
Assignment
Single Group Assignment
Trial Arms
1