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

NCT ID: NCT04047251

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-14
• Study Completion Date: 2026-07-31

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

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: Two additional cohorts are planned. Cohort E1: advanced ovarian cancer and Cohort E5 Merkel cell carcinoma. 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.

Conditions

Advanced Solid Tumors; Merkel Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

FF-10850 Topotecan Liposome Injection

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

FF-10850 Topotecan Liposome Injection

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

FF-10850 Topotecan Liposome Injection

Intervention Type: DRUG

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

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

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

Group Type: EXPERIMENTAL

FF-10850 Topotecan Liposome Injection

Intervention Type: DRUG

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

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

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

Group Type: EXPERIMENTAL

FF-10850 Topotecan Liposome Injection

Intervention Type: DRUG

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

Interventions

FF-10850 Topotecan Liposome Injection

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

Intervention Type: DRUG

Other Intervention Names

FF-10850

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujifilm Pharmaceuticals U.S.A., Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

HonorHealth

Scottsdale, Arizona, United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37683276 (View on PubMed)

Other Identifiers

FF10850US101

Identifier Type: -

Identifier Source: org_study_id