Trial Condition(s):

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 (ROCOCO)

Bayer Identifier:

19774

ClinicalTrials.gov Identifier:

NCT03517956

EudraCT Number:

2018-000419-26

Study Completed

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.

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 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.
Exclusion Criteria
- 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
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Phase
1
Could I receive a placebo?
No
Products
Rogaratinib (BAY1163877)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Universitätsklinikum Köln

Köln, Germany, 50937

Status
Completed
 
Locations

Klinikum der Universität Würzburg

Würzburg, Germany, 97080

Status
Completed
 
Locations

Krankenhaus Nordwest

Frankfurt, Germany, 60488

Status
Completed
 
Locations

Memorial Sloan-Kettering Cancer Center

New York, United States, 10065

Status
Completed
 
Locations

Dana-Farber Cancer Institute

Boston, United States, 02215

Status
Completed
 
Locations

Barbara Ann Karmanos Cancer Institute - Detroit

Detroit, United States, 48201

Status
Completed
 
Locations

Northwestern University

Chicago, United States, 60611

Status
Completed
 
Locations

CU Saint-Luc/UZ St-Luc

BRUXELLES - BRUSSEL, Belgium, 1200

Status
Completed
 
Locations

CHU de Liège

LIEGE, Belgium, 4000

Status
Completed
 
Locations

UZ Antwerpen

EDEGEM, Belgium, 2650

Status
Completed
 
Locations

Samsung Medical Center

Seoul, South Korea, 06351

Status
Completed
 
Locations

Severance Hospital, Yonsei University Health System

Seoul, South Korea, 03722

Status
Completed
 
Locations

Asan Medical Center

Seoul, South Korea, 05505

Status
Completed
 
Locations

National University Hospital

Singapore, Singapore, 119074

Status
Completed
 
Locations

National Cancer Center Singapore

Singapore, Singapore, 169610

Status
Completed
 
Locations

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08035

Status
Completed
 
Locations

Hospital Clínico Universitario de Valencia

Valencia, Spain, 46010

Status
Completed
 
Locations

USC Norris Hospital and Clinics

Los Angeles, United States, 90033

Status
Completed
 
Locations

University of Maryland

Baltimore, United States, 21201

Status
Completed
 
Locations

Tyler Cancer Center

Tyler, United States, 75702

Status
Completed
 

Trial Design