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Trial record 1 of 1 for:    FF-10850
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A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04047251
Recruitment Status : Recruiting
First Posted : August 6, 2019
Last Update Posted : December 19, 2019
Sponsor:
Information provided by (Responsible Party):
Fujifilm Pharmaceuticals U.S.A., Inc.

Tracking Information
First Submitted Date  ICMJE August 1, 2019
First Posted Date  ICMJE August 6, 2019
Last Update Posted Date December 19, 2019
Actual Study Start Date  ICMJE November 14, 2019
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Determine incidence of Treatment Emergent Adverse Events [ Time Frame: 4 years ]
    Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs)
  • Identify dose-limiting toxicities (DLT) of FF-10850 [ Time Frame: 4 years ]
    DLT is defined as any adverse event at least possibly related to FF-10850, and meeting specified DLT criteria
  • Determine maximun tolerated dose (MTD) of FF-10850 [ Time Frame: 4 years ]
    MTD is defined as the next lower dose of a cohort where patients experienced a DLT
  • Determine recommended Phase 2 dose (RP2D) FF-10850 [ Time Frame: 4 years ]
    The highest dose level below the dose level eliciting DLT in ≥ 2 patients will be declared the MTD. The RP2D will be chosen based on the MTD or on PK and biological activity if an MTD has not been determined.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Cmax [ Time Frame: 4 years ]
    Measurement of maximum plasma concentration
  • Characterize the pharmacokinetics (PK) of FF-10850 in plasma: tmax [ Time Frame: 4 years ]
    Measurement of time to reach Cmax
  • Characterize the pharmacokinetics (PK) of FF-10850 in plasma: t1/2 [ Time Frame: 4 years ]
    Measurement of the elimination half-life
  • Characterize the pharmacokinetics (PK) of FF-10850 in plasma: AUC [ Time Frame: 4 years ]
    Measurement of the area under the curve of plasma concentration versus time profile
  • Characterize the pharmacokinetics (PK) of FF-10850 in plasma: MRT [ Time Frame: 4 years ]
    Measurement of the mean residence time adjusted for duration of infusion
  • Characterize the pharmacokinetics (PK) of FF-10850 in plasma: CL [ Time Frame: 4 years ]
    Measurement of the total plasma clearance
  • Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Vss [ Time Frame: 4 years ]
    Measurement of the steady-state volume of distribution for total topotecan
  • Determine objective response rate (ORR) [ Time Frame: 4 years ]
    classified for solid tumors via RECIST v.1.1
  • Determine the duration of response (DOR) [ Time Frame: 4 years ]
    Duration of Response is calculated from the date of first response to the date of progression or death.
  • Determine the time to progression (TTP) [ Time Frame: 4 years ]
    Time to progression is calculated from the date of first treatment to the date of first progression
  • Evaluate progression-free survival (PFS) [ Time Frame: 4 years ]
    Progression-free survival will be calculated from the date of first treatment to the date of progression or death
  • Evaluate overall survival (OS) (expansion cohorts only) [ Time Frame: 4 years ]
    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.
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 A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Open label, dose escalation
Masking: None (Open Label)
Masking Description:
None, open label
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Drug: FF-10850 Topotecan Liposome Injection
FF-10850 to be diluted and infused over 60 minutes.
Study Arms  ICMJE
  • Experimental: Cohort 1: Treatment at Dose Level 1
    FF-10850 Topotecan Liposome Injection, Dose Level 1 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
    Intervention: Drug: FF-10850 Topotecan Liposome Injection
  • Experimental: Cohort 2: Treatment at Dose Level 2
    FF-10850 Topotecan Liposome Injection, Dose Level 2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
    Intervention: Drug: FF-10850 Topotecan Liposome Injection
  • Experimental: Cohort 3: Treatment at Dose Level 3
    FF-10850 Topotecan Liposome Injection, Dose Level 3 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
    Intervention: Drug: FF-10850 Topotecan Liposome Injection
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: August 5, 2019)
96
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2025
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
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: FPHU Study Coordinator fphucontact@fujifilm.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04047251
Other Study ID Numbers  ICMJE FF10850US101
Has Data Monitoring Committee Yes
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: undecided
Responsible Party Fujifilm Pharmaceuticals U.S.A., Inc.
Study Sponsor  ICMJE Fujifilm Pharmaceuticals U.S.A., Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fujifilm Pharmaceuticals U.S.A., Inc.
Verification Date December 2019

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