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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

NCT03517956

Description:

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 locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

Related Conditions:
  • Malignant Solid Tumor
  • Transitional Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: 19774
  • SECONDARY ID: 2018-000419-26
  • NCT ID: NCT03517956

Conditions

  • Advanced or Metastatic Solid Tumor

Interventions

DrugSynonymsArms
Rogaratinib (BAY1163877)Patients with FGFR1-4 - positive solid tumors
Copanlisib (BAY80-6946)Patients with FGFR1-4 - positive solid tumors

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Patients with FGFR1-4 - positive solid tumorsExperimentalDose 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.
  • Rogaratinib (BAY1163877)
  • Copanlisib (BAY80-6946)

Eligibility Criteria

        Inclusion Criteria:

          -  High FGFR mRNA expression levels (RNAscope score of 3+ or 4+; 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.

          -  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.

        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).

          -  Symptomatic metastatic brain or meningeal 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse events (TEAEs)
Time Frame:Up to 32 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Objective response rate (ORR)
Time Frame:Up to 32 months
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:Up to 32 months
Safety Issue:
Description:
Measure:Duration of response (DOR) for Partial Response and Complete Response
Time Frame:Up to 32 months
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Up to 32 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Up to 32 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Phase I
  • Locally advanced or metastatic solid tumor
  • Urothelial cancer
  • FGFR inhibitor

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