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JOURNAL ONKOLOGIE – STUDIE

ROCOCO 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

Rekrutierend

NCT-Nummer:
NCT03517956

Studienbeginn:
Juli 2018

Letztes Update:
23.10.2019

Wirkstoff:
Rogaratinib (BAY1163877), Copanlisib (BAY80-6946)

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Bayer

Collaborator:
-

Kontakt

Bayer Clinical Trials Contact
Kontakt:
Phone: (+)1-888-84 22937
E-Mail: clinical-trials-contact@bayer.com
» Kontaktdaten anzeigen

Studienlocations (3 von 29)

Onkologisches Zentrum Krankenhaus Nordwest
Steinbacher Hohl 2-26
60488 Frankfurt am Main
DeutschlandRekrutierend» Google-Maps
Universitätsklinikum Köln
50937 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Universitätsklinikum Hamburg Eppendorf (UKE)
20246 Hamburg
(Hamburg)
GermanyZurückgezogen» Google-Maps
Klinikum der Universität Würzburg
97080 Würzburg
(Bayern)
GermanyRekrutierend» Google-Maps
USC Norris Hospital and Clinics
90033 Los Angeles
United StatesRekrutierend» Google-Maps
Northwestern University
60611 Chicago
United StatesRekrutierend» Google-Maps
University of Maryland
12101 Baltimore
United StatesRekrutierend» Google-Maps
Dana-Farber Cancer Institute
02215 Boston
United StatesRekrutierend» Google-Maps
Barbara Ann Karmanos Cancer Institute
48201 Detroit
United StatesRekrutierend» Google-Maps
Comprehensive Cancer Centers of Nevada
89169 Las Vegas
United StatesNoch nicht rekrutierend» Google-Maps
Memorial Sloan-Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
Prisma Health
29605 Greenville
United StatesNoch nicht rekrutierend» Google-Maps
Texas Oncology- Austin Midtown
78705 Austin
United StatesNoch nicht rekrutierend» Google-Maps
CU Saint-Luc/UZ St-Luc
1200 Bruxelles - Brussel
BelgiumRekrutierend» Google-Maps
Centre Oscar Lambret - Lille
59020 LILLE cedex
FranceZurückgezogen» Google-Maps
Asan Medical Center
05505 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Samsung Medical Center
06351 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Yonsei University College of Medicine
120-752 Seoul
Korea, Republic ofRekrutierend» Google-Maps
National University Hospital
119074 Singapore
SingaporeRekrutierend» Google-Maps
Ciutat Sanitària i Universitaria de la Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
Hospital Clínic i Provincial de Barcelona
08036 Barcelona
SpainZurückgezogen» Google-Maps
Hospital General Universitario Gregorio Marañón
28007 Madrid
SpainZurückgezogen» Google-Maps
MD Anderson International Espanya, S.A.
28033 Madrid
SpainZurückgezogen» Google-Maps
Hospital Clínico Universitario de Valencia
46010 Valencia
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

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.

Ein-/Ausschlusskriterien

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).

Studien-Rationale

Primary outcome:

1. Incidence of treatment-emergent adverse events (TEAEs) (Time Frame - Up to 32 months)

2. Incidence of drug-related TEAEs (Time Frame - Up to 32 months)

3. Incidence of treatment-emergent serious adverse events (TESAEs) (Time Frame - Up to 32 months)

4. Incidence of Dose-limiting toxicities (DLTs) (Time Frame - Approximately 10 months)

5. Objective response rate (ORR) at recommended dose (Time Frame - Up to 22 months):
ORR in patients receiving the recommended dose of the rogaratinib-copanlisib-combination during the dose expansion part

Secondary outcome:

1. Maximum plasma concentration of Copanlisib (Cmax) (Time 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)

2. Area under the plasma concentration versus time curve of Copanlisib (AUC (0-48)) (Time 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)

3. Area under the plasma concentration versus time curve of Rogaratinib (AUC (0-8)) (Time 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)

4. Maximum plasma concentration of Rogaratinib (Cmax) (Time 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)

5. Objective response rate (ORR) (Time Frame - Up to 32 months)

6. Disease control rate (DCR) (Time Frame - Up to 32 months)

7. Duration of response (DOR) for Partial Response and Complete Response (Time Frame - Up to 32 months)

8. Progression-free survival (PFS) (Time Frame - Up to 32 months)

9. Overall survival (OS) (Time Frame - Up to 32 months)

Geprüfte Regime

  • Rogaratinib (BAY1163877):
    Dose escalation: Starting dose is rogaratinib 400 mg twice daily (b.i.d.) in continuous 28-day cycles from Cycle 1 Day 3 onwards. Dose expansion: With dose identified in dose escalation part.
  • Copanlisib (BAY80-6946):
    Dose escalation: Starting dose is 45 mg on Days 1, 8 and 15 of each 28-day cycle. Dose expansion: With dose identified in dose escalation part.

Quelle: ClinicalTrials.gov


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