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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)

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ClinicalTrials.gov Identifier: NCT03517956
Recruitment Status : Recruiting
First Posted : May 8, 2018
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE May 3, 2018
First Posted Date  ICMJE May 8, 2018
Last Update Posted Date September 4, 2019
Actual Study Start Date  ICMJE July 25, 2018
Estimated Primary Completion Date September 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2019)
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 32 months ]
  • Incidence of drug-related TEAEs [ Time Frame: Up to 32 months ]
  • Incidence of treatment-emergent serious adverse events (TESAEs) [ Time Frame: Up to 32 months ]
  • Incidence of Dose-limiting toxicities (DLTs) [ Time Frame: Approximately 10 months ]
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 32 months ]
  • Incidence of drug-related TEAEs [ Time Frame: Up to 32 months ]
  • Incidence of treatment-emergent serious adverse events (TESAEs) [ Time Frame: Up to 32 months ]
  • Incidence of Dose-limiting toxicities (DLTs) [ Time Frame: Approximately 10 months ]
Change History Complete list of historical versions of study NCT03517956 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Objective response rate (ORR) [ Time Frame: Up to 32 months ]
  • Disease control rate (DCR) [ Time Frame: Up to 32 months ]
  • Duration of response (DOR) for Partial Response and Complete Response [ Time Frame: Up to 32 months ]
  • Progression-free survival (PFS) [ Time Frame: Up to 32 months ]
  • Overall survival (OS) [ Time Frame: Up to 32 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced or Metastatic Solid Tumor
Intervention  ICMJE
  • Drug: 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.

  • Drug: 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.

Study Arms  ICMJE Experimental: Patients with FGFR1-4 - positive solid tumors

Dose escalation:

The starting dose of the combination will be escalated in a stepwise fashion, escalating one drug at a time.

Dose expansion (urothelial cancer):

Patients in the dose expansion will be treated with the combination identified in the dose escalation part of the study.

Interventions:
  • Drug: Rogaratinib (BAY1163877)
  • Drug: Copanlisib (BAY80-6946)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2018)
65
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 29, 2021
Estimated Primary Completion Date September 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Korea, Republic of,   Singapore,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03517956
Other Study ID Numbers  ICMJE 19774
2018-000419-26 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP