Clinical trial NCT04047251: A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Merkel Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Merkel Cell Carcinoma
Lead sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-06
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open label, dose escalation
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Determine incidence of Treatment Emergent Adverse Events
timeFrame: 4 years
measure: Identify dose-limiting toxicities (DLT) of FF-10850
timeFrame: 4 years
measure: Determine maximun tolerated dose (MTD) of FF-10850
timeFrame: 4 years
measure: Determine recommended Phase 2 dose (RP2D) FF-10850
timeFrame: 4 years
Secondary outcomes:
measure: Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Cmax
timeFrame: 4 years
measure: Characterize the pharmacokinetics (PK) of FF-10850 in plasma: tmax
timeFrame: 4 years
measure: Characterize the pharmacokinetics (PK) of FF-10850 in plasma: t1/2
timeFrame: 4 years
measure: Characterize the pharmacokinetics (PK) of FF-10850 in plasma: AUC
timeFrame: 4 years
measure: Characterize the pharmacokinetics (PK) of FF-10850 in plasma: MRT
timeFrame: 4 years
measure: Characterize the pharmacokinetics (PK) of FF-10850 in plasma: CL
timeFrame: 4 years
measure: Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Vss
timeFrame: 4 years
measure: Determine objective response rate (ORR)
timeFrame: 4 years
measure: Determine the duration of response (DOR)
timeFrame: 4 years
measure: Determine the time to progression (TTP)
timeFrame: 4 years
measure: Evaluate progression-free survival (PFS)
timeFrame: 4 years
measure: Evaluate overall survival (OS) (expansion cohorts only)
timeFrame: 4 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Boston
country: United States
facility: Dana Farber Cancer Institute (DFCI)
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
Study officials:
References: