Clinical Trials /

A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors

NCT04047251

Description:

To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended Phase 2 dose (RP2D) of FF-10850 (topotecan liposome injection) in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors
  • Official Title: A Phase 1 Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Ovarian and Cervical Carcinoma, Sarcomas, and Neuroendocrine Tumors Including Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: FF10850US101
  • NCT ID: NCT04047251

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
FF-10850 Topotecan Liposome InjectionCohort 1: Treatment at Dose Level 1

Purpose

To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended Phase 2 dose (RP2D) of FF-10850 (topotecan liposome injection) in patients with advanced solid tumors.

Detailed Description

      Dose-escalation Phase: Approximately 48 patients are planned for the dose-escalation phase,
      with at least 6 patients treated at the RP2D.

      Cohort Expansion Phase: Four additional cohorts of 12 patients each are planned. Cohort E1:
      advanced ovarian cancer; Cohort E2: advanced cervical cancer, Cohort E3: advanced sarcomas,
      and Cohort E4: advanced neuroendocrine tumors including small cell lung cancer. Each cohort
      will be treated at the RP2D.

      In each cohort, FF-10850 will be administered intravenously (IV) until progression of
      disease, observation of unacceptable AEs, or, after discussion between the Investigator and
      the Medical Monitor, changes in the patient's condition that prevent further study
      participation. A sufficient number of cohorts will be enrolled to identify the RP2D.

      There will be 3 initial dose levels in this study. FF-10850 will be diluted and infused over
      60 minutes.

      Approximately 96 patients are planned for the entire trial.

      It is anticipated that approximately 4 centers will participate in the dose-escalation phase,
      with an expansion to approximately 10 centers in the cohort expansion phase. Accrual for the
      dose-escalation and expansion phases is expected to be approximately 3 years, with patients
      followed every 3 months from the last dose of study treatment to assess survival.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Treatment at Dose Level 1ExperimentalFF-10850 Topotecan Liposome Injection, Dose Level 1 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
  • FF-10850 Topotecan Liposome Injection
Cohort 2: Treatment at Dose Level 2ExperimentalFF-10850 Topotecan Liposome Injection, Dose Level 2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
  • FF-10850 Topotecan Liposome Injection
Cohort 3: Treatment at Dose Level 3ExperimentalFF-10850 Topotecan Liposome Injection, Dose Level 3 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
  • FF-10850 Topotecan Liposome Injection

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet all the following criteria to participate in the study:

          1. Males and females ≥ 18 years of age

          2. Dose-escalation phase: Histologically or cytologically confirmed metastatic and/or
             unresectable solid tumor, relapsed or refractory to standard therapy, or for which no
             standard therapy is available that is expected to improve survival by at least 3
             months

          3. At least 3 weeks beyond the last chemotherapy (or 3 half-lives, whichever is shorter),
             radiotherapy, major surgery, or experimental treatment, and recovered from all acute
             toxicities (≤ Grade 1), prior to the first dose of FF-10850

          4. Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1

          5. Life expectancy of ≥ 3 months

          6. Adequate hematologic parameters without ongoing transfusion support:

               -  Hemoglobin (Hb) ≥ 9 g/dL

               -  Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells/L

               -  Platelets ≥ 100 × 109 cells/L

          7. Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 50 mL/minute by either
             the Cockcroft-Gault formula or as measured by a 24-hour urine collection

          8. Total bilirubin ≤ 2 × ULN unless due to Gilbert's disease; patients with Gilbert's
             disease who have a total bilirubin > 6 mg/dL are to be excluded

          9. ALT and AST ≤ 2.5 times ULN, or < 5 × ULN for patients with liver metastases

         10. QT interval corrected for rate (QT interval corrected for rate using Fridericia's
             Correction Formula, QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG
             obtained at Screening and confirmed pre-treatment on Cycle 1 Day 1.

         11. Patient must be willing to undergo a tumor biopsy, if the patient has a
             biopsy-accessible tumor

        Exclusion Criteria:

          1. Patients who have not received standard/approved therapies expected to improve
             survival by at least 3 months

          2. History of severe hypersensitivity reactions to topotecan

          3. Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia,
             myocardial infarction, unstable angina or heart disease defined by the New York Heart
             Association (NYHA) Class III or Class IV or hereditary long QT syndrome

          4. Concomitant medication(s) that may cause QTc prolongation or induce Torsades de
             Pointes, except for antimicrobials that are used as standard of care to prevent or
             treat infections and other such drugs that are considered by the Investigator to be
             essential for patient care

          5. Active central nervous system (CNS) malignant disease in patients with a history of
             CNS malignancy. Patients with previously treated stable brain metastases are allowed
             if they have been stable off steroid therapy for at least 4 weeks.

          6. Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface
             antigen (HBsAg) or hepatitis C virus (HCV)

          7. Active infection requiring intravenous (IV) antibiotic usage within the last week
             prior to study treatment

          8. Any other medical intervention or other condition which, in the opinion of the
             Principal Investigator, could compromise adherence to study requirements or confound
             the interpretation of study results

          9. Pregnant or breast-feeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine incidence of Treatment Emergent Adverse Events
Time Frame:4 years
Safety Issue:
Description:Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome Measures

Measure:Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Cmax
Time Frame:4 years
Safety Issue:
Description:Measurement of maximum plasma concentration
Measure:Characterize the pharmacokinetics (PK) of FF-10850 in plasma: tmax
Time Frame:4 years
Safety Issue:
Description:Measurement of time to reach Cmax
Measure:Characterize the pharmacokinetics (PK) of FF-10850 in plasma: t1/2
Time Frame:4 years
Safety Issue:
Description:Measurement of the elimination half-life
Measure:Characterize the pharmacokinetics (PK) of FF-10850 in plasma: AUC
Time Frame:4 years
Safety Issue:
Description:Measurement of the area under the curve of plasma concentration versus time profile
Measure:Characterize the pharmacokinetics (PK) of FF-10850 in plasma: MRT
Time Frame:4 years
Safety Issue:
Description:Measurement of the mean residence time adjusted for duration of infusion
Measure:Characterize the pharmacokinetics (PK) of FF-10850 in plasma: CL
Time Frame:4 years
Safety Issue:
Description:Measurement of the total plasma clearance
Measure:Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Vss
Time Frame:4 years
Safety Issue:
Description:Measurement of the steady-state volume of distribution for total topotecan
Measure:Determine objective response rate (ORR)
Time Frame:4 years
Safety Issue:
Description:classified for solid tumors via RECIST v.1.1
Measure:Determine the duration of response (DOR)
Time Frame:4 years
Safety Issue:
Description:Duration of Response is calculated from the date of first response to the date of progression or death.
Measure:Determine the time to progression (TTP)
Time Frame:4 years
Safety Issue:
Description:Time to progression is calculated from the date of first treatment to the date of first progression
Measure:Evaluate progression-free survival (PFS)
Time Frame:4 years
Safety Issue:
Description:Progression-free survival will be calculated from the date of first treatment to the date of progression or death
Measure:Evaluate overall survival (OS) (expansion cohorts only)
Time Frame:4 years
Safety Issue:
Description:Overall survival will be calculated from the date of first treatment to the date of death from any cause; patients who do not experience death will be censored at the last follow-up time.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fujifilm Pharmaceuticals U.S.A., Inc.

Last Updated

August 11, 2020