A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Merkel Cell Carcinoma

NCT04047251 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: FF10850US101
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 7

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 including Merkel Cell Carcinoma

Conditions

Advanced Solid Tumors; Merkel Cell Carcinoma

Outcome Measures

Primary Outcomes (4)

• Determine incidence of Treatment Emergent Adverse Events

  Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs)

  4 years

• Identify dose-limiting toxicities (DLT) of FF-10850

  DLT is defined as any adverse event at least possibly related to FF-10850, and meeting specified DLT criteria

  4 years

• Determine maximun tolerated dose (MTD) of FF-10850

  MTD is defined as the next lower dose of a cohort where patients experienced a DLT

  4 years

• Determine recommended Phase 2 dose (RP2D) FF-10850

  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.

  4 years

Secondary Outcomes (12)

• Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Cmax

  4 years

• Characterize the pharmacokinetics (PK) of FF-10850 in plasma: tmax

  4 years

• Characterize the pharmacokinetics (PK) of FF-10850 in plasma: t1/2

  4 years

• Characterize the pharmacokinetics (PK) of FF-10850 in plasma: AUC

  4 years

• Characterize the pharmacokinetics (PK) of FF-10850 in plasma: MRT

  4 years

Study Arms (5)

Cohort 1: Treatment at Dose Level 1

EXPERIMENTAL

FF-10850 Topotecan Liposome Injection, Dose Level 1 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Drug: FF-10850 Topotecan Liposome Injection

Cohort 2: Treatment at Dose Level 2

EXPERIMENTAL

FF-10850 Topotecan Liposome Injection, Dose Level 2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Drug: FF-10850 Topotecan Liposome Injection

Cohort 3: Treatment at Dose Level 3

EXPERIMENTAL

FF-10850 Topotecan Liposome Injection, Dose Level 3 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Drug: FF-10850 Topotecan Liposome Injection

Cohort E1: Treatment at Recommended Phase 2 Dose (RP2D)

EXPERIMENTAL

For patients with advanced ovarian cancer: FF-10850 Topotecan Liposome Injection, RP2D administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Drug: FF-10850 Topotecan Liposome Injection

Cohort E5: Treatment at Recommended Phase 2 Dose (RP2D)

EXPERIMENTAL

For patients with advanced Merkel cell carcinoma: FF-10850 Topotecan Liposome Injection, RP2D administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Drug: FF-10850 Topotecan Liposome Injection

Interventions

FF-10850 Topotecan Liposome Injection DRUG

FF-10850 to be diluted and infused over 60 minutes.

Also known as: FF-10850

Cohort 1: Treatment at Dose Level 1; Cohort 2: Treatment at Dose Level 2; Cohort 3: Treatment at Dose Level 3; Cohort E1: Treatment at Recommended Phase 2 Dose (RP2D); Cohort E5: Treatment at Recommended Phase 2 Dose (RP2D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all the following criteria to participate in the study:
• Males and females ≥ 18 years of age
• 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
• 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
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Life expectancy of ≥ 3 months
• 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
• 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
• 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
• ALT and AST ≤ 2.5 times ULN, or \< 5 × ULN for patients with liver metastases
• 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.
• Patient must be willing to undergo a tumor biopsy, if the patient has a biopsy-accessible tumor

You may not qualify if:

• Patients who have not received standard/approved therapies expected to improve survival by at least 3 months
• History of severe hypersensitivity reactions to topotecan
• 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
• 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
• 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.
• Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
• Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment
• 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
• Pregnant or breast-feeding

Sponsors & Collaborators

• Fujifilm Pharmaceuticals U.S.A., Inc.: lead

Study Sites (7)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43221, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Shimoyama S, Okada K, Kimura T, Morohashi Y, Nakayama S, Kemmochi S, Makita-Suzuki K, Matulonis UA, Mori M. FF-10850, a Novel Liposomal Topotecan Achieves Superior Antitumor Activity via Macrophage- and Ammonia-Mediated Payload Release in the Tumor Microenvironment. Mol Cancer Ther. 2023 Dec 1;22(12):1454-1464. doi: 10.1158/1535-7163.MCT-23-0099.

  PMID: 37683276 DERIVED

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None, open label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, dose escalation

Study Record Dates

• First Submitted: August 1, 2019
• First Posted: August 6, 2019
• Study Start: November 14, 2019
• Primary Completion: December 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 4, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)