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.
Overal Status | Start Date | Phase | Study Type |
---|---|---|---|
Recruiting | July 25, 2018 | Phase 1 | Interventional |
Primary Outcome 1 - Measure: Incidence of treatment-emergent adverse events (TEAEs)
Primary Outcome 1 - Time Frame: Up to 32 months
Primary Outcome 2 - Measure: Incidence of drug-related TEAEs
Primary Outcome 2 - Time Frame: Up to 32 months
Primary Outcome 3 - Measure: Incidence of treatment-emergent serious adverse events (TESAEs)
Primary Outcome 3 - Time Frame: Up to 32 months
Primary Outcome 4 - Measure: Incidence of Dose-limiting toxicities (DLTs)
Primary Outcome 4 - Time Frame: Approximately 10 months
Primary Outcome 5 - Measure: Objective response rate (ORR) at recommended dose
Primary Outcome 5 - Time Frame: Up to 22 months
Criteria:
Inclusion Criteria:
- 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 m2 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.
Exclusion Criteria:
- Previous or concurrent cancer that is distinct from tumor for which the patient is
enrolled in study, with exceptions
- 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).
Show More
Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Bayer Clinical Trials Contact
Phone: (+)1-888-84 22937
Email: clinical-trials-contact@bayer.com
Facility | Status | Contact |
---|---|---|
USC Norris Hospital and Clinics Los Angeles, California 90033 United States |
Recruiting | |
Northwestern University Chicago, Illinois 60611 United States |
Recruiting | |
University of Maryland Baltimore, Maryland 12101 United States |
Recruiting | |
Dana-Farber Cancer Institute Boston, Massachusetts 02215 United States |
Recruiting | |
Barbara Ann Karmanos Cancer Institute Detroit, Michigan 48201 United States |
Recruiting | |
Comprehensive Cancer Centers of Nevada Las Vegas, Nevada 89169 United States |
Not yet recruiting | |
Memorial Sloan-Kettering Cancer Center New York, New York 10065 United States |
Recruiting | |
Prisma Health Greenville, South Carolina 29605 United States |
Not yet recruiting | |
Texas Oncology- Austin Midtown Austin, Texas 78705 United States |
Not yet recruiting | |
Tyler Cancer Center Tyler, Texas 75702 United States |
Recruiting | |
CU Saint-Luc/UZ St-Luc Bruxelles - Brussel, 1200 Belgium |
Recruiting | |
UZ Antwerpen Edegem, 2650 Belgium |
Recruiting | |
CHU de Liège Liege, 4000 Belgium |
Recruiting | |
Centre Oscar Lambret - Lille LILLE cedex, 59020 France |
Withdrawn | |
Centre Léon Bérard Lyon Cedex, 69008 France |
Withdrawn | |
Krankenhaus Nordwest Frankfurt, Hessen 60488 Germany |
Recruiting | |
Universitätsklinikum Köln Köln, Nordrhein-Westfalen 50937 Germany |
Recruiting | |
Universitätsklinikum Hamburg Eppendorf (UKE) Hamburg, 20246 Germany |
Withdrawn | |
Klinikum der Universität Würzburg Würzburg, 97080 Germany |
Recruiting | |
Asan Medical Center Seoul, 05505 Korea, Republic of |
Recruiting | |
Samsung Medical Center Seoul, 06351 Korea, Republic of |
Recruiting | |
Yonsei University College of Medicine Seoul, 120-752 Korea, Republic of |
Recruiting | |
National University Hospital Singapore, 119074 Singapore |
Recruiting | |
National Cancer Center Singapore, 169610 Singapore |
Recruiting | |
Ciutat Sanitària i Universitaria de la Vall d'Hebron Barcelona, 08035 Spain |
Recruiting | |
Hospital Clínic i Provincial de Barcelona Barcelona, 08036 Spain |
Withdrawn | |
Hospital General Universitario Gregorio Marañón Madrid, 28007 Spain |
Withdrawn | |
MD Anderson International Espanya, S.A. Madrid, 28033 Spain |
Withdrawn | |
Hospital Clínico Universitario de Valencia Valencia, 46010 Spain |
Recruiting |