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

Advanced Solid Tumors Clinical Trial

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 and Merkel Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04047251
• Other study ID #: FF10850US101
• Status: Recruiting
• Phase: Phase 1
• Start date: November 14, 2019
• Est. completion date: July 2026

Study information

• Verified date: June 2024
• Source: Fujifilm Pharmaceuticals U.S.A., Inc.
• Contact: FPHU Study Coordinator
• Email: fphucontact[@]fujifilm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: July 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• FF-10850 Topotecan Liposome Injection
FF-10850 to be diluted and infused over 60 minutes.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	HonorHealth	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Fujifilm Pharmaceuticals U.S.A., Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine incidence of Treatment Emergent Adverse Events	Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs)	4 years
Primary	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
Primary	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
Primary	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	Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Cmax	Measurement of maximum plasma concentration	4 years
Secondary	Characterize the pharmacokinetics (PK) of FF-10850 in plasma: tmax	Measurement of time to reach Cmax	4 years
Secondary	Characterize the pharmacokinetics (PK) of FF-10850 in plasma: t1/2	Measurement of the elimination half-life	4 years
Secondary	Characterize the pharmacokinetics (PK) of FF-10850 in plasma: AUC	Measurement of the area under the curve of plasma concentration versus time profile	4 years
Secondary	Characterize the pharmacokinetics (PK) of FF-10850 in plasma: MRT	Measurement of the mean residence time adjusted for duration of infusion	4 years
Secondary	Characterize the pharmacokinetics (PK) of FF-10850 in plasma: CL	Measurement of the total plasma clearance	4 years
Secondary	Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Vss	Measurement of the steady-state volume of distribution for total topotecan	4 years
Secondary	Determine objective response rate (ORR)	classified for solid tumors via RECIST v.1.1	4 years
Secondary	Determine the duration of response (DOR)	Duration of Response is calculated from the date of first response to the date of progression or death.	4 years
Secondary	Determine the time to progression (TTP)	Time to progression is calculated from the date of first treatment to the date of first progression	4 years
Secondary	Evaluate progression-free survival (PFS)	Progression-free survival will be calculated from the date of first treatment to the date of progression or death	4 years
Secondary	Evaluate overall survival (OS) (expansion cohorts only)	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.	4 years