A Phase 1 Dose-escalation Study of FF-10832 for Treatment of Solid Tumors

A Phase 1 Dose-escalation Study of FF-10832 for the Treatment of Advanced Solid Tumors

To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLT) and recommended Phase 2 dose (RP2D) in patients who receive FF-10832 (Gemcitabine Liposome Injection) for treatment of advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: FF-10832 Gemcitabine Liposome Injection

Detailed Description

Dose-escalation Phase:

Eligible patients will receive FF-10832 in 28 day or 21 day cycles. Dosing will continue until progression of disease, observation of unacceptable adverse events, intercurrent illness, or changes in the patient's condition that prevents further study participation after discussion between the Investigator and the Medical Monitor. A number of cohorts will be enrolled sufficient to determine the MTD and to identify the RP2D.

Expansion Phase:

One cohort of biliary tract cancer will enroll up to 15 patients in a 21 day cycle.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: FPHU Study Coordinator; Email: fphucontact@fujifilm.com

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • Honor Health Research Institute
    • Tucson, Arizona, United States, 85719
      • Recruiting
      • University of Arizona Cancer Center
  • California
    • Newport Beach, California, United States, 92658
      • Completed
      • Hoag Memorial Hospital Comprehensive Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Completed
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Completed
      • MD Anderson Cancer Research Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Recruiting
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females ≥ 18 years of age
2. Histologically or cytologically confirmed metastatic 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 three 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-10832

4. Cohort expansion phase: (biliary tract cancer):

   • Histologically or cytologically confirmed cholangiocarcinoma or gall bladder carcinoma that is metastatic pancreatic adenocarcinoma following progression or relapseor unresectable
   • Measurable disease by RECIST 1.1
   • Progressed on at least one prior regimengemcitabine-cisplatin therapy or gemcitabine-based therapy if unable to tolerate cisplatin. Adjuvant therapy counts as such therapy.
   • Progressed on, declined on, or was ineligible for therapies directed against fibroblast growth factor (FGFR) and/or isocitrate dehydrogenase (IDH) mutations for tumors appropriately treated with such therapies
   • No more than 3 prior systemic therapies for their tumor. Please contact the medical monitor if there are any questions about eligibility.
   • A serum albumin level ≥ 3 g/dL on entry to the study
5. Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1
6. Life expectancy of ≥ 3 months
7. Ability to provide written informed consent

Exclusion Criteria:

1. Patients who have not received standard/approved therapies expected to improve survival by at least 3 months
2. Prior hypersensitivity to gemcitabine
3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Treatment at 1.2 mg/m2; FF-10832 Gemcitabine Liposome Injection, 1.2 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle	Drug: FF-10832 Gemcitabine Liposome Injection; FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes; Other Names: FF-10832
Experimental: Cohort 2: Treatment at 2.4 mg/m2; FF-10832 Gemcitabine Liposome Injection, 2.4 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle	Drug: FF-10832 Gemcitabine Liposome Injection; FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes; Other Names: FF-10832
Experimental: Cohort 3: Treatment at 4.8 mg/m2; FF-10832 Gemcitabine Liposome Injection, 4.8 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle	Drug: FF-10832 Gemcitabine Liposome Injection; FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes; Other Names: FF-10832
Experimental: Cohort 4: Treatment at 8 mg/m2; FF-10832 Gemcitabine Liposome Injection, 8 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle	Drug: FF-10832 Gemcitabine Liposome Injection; FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes; Other Names: FF-10832
Experimental: Expansion Cohort: Treatment at Recommended Phase 2 Dose (RP2D); For patients with biliary tract cancer: FF-10832 Gemcitabine Liposome Injection, RP2D administered intravenously (IV) on Day 1 of each 21-day cycle	Drug: FF-10832 Gemcitabine Liposome Injection; FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes; Other Names: FF-10832

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine incidence of Treatment Emergent Adverse Events (TEAE)	Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs)	2.5 years
Identify dose-limiting toxicities (DLT) of FF-10832	DLT is defined as any adverse event at least possibly related to FF-10832, and meeting specified DLT criteria	2.5 years
Determine maximun tolerated dose (MTD) of FF-10832	MTD is defined as the next lower dose of a cohort where patients experienced a DLT	2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Assessment by CT or MRI scan for solid tumors	Disease assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1), clinical benefit is defined as best response of complete response (CR), partial response (PR), stable disease (SD) or disease progression (DP)	2.5 years
Disease Assessment by CT or MRI + PET scan for pancreatic cancer	For solid tumors assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1), clinical benefit is defined as best response of complete response (CR), partial response (PR), stable disease (SD) or disease progression (DP). European Organisation for Research and Treatment of Cancer (EORTC) criteria will be utilized for PET response assessments.	2.5 years
Duration of Response	Duration of Response is calculated from the date of first response to the date of progression or death	2.5 years
Duration of Stable Disease	Duration of Stable Disease is the length of time from the start of the treatment until the criteria for progression are met	2.5 years
Time to progression (TTP)	Time to progression is calculated from the date of first treatment to the date of first progression	2.5 years
Progression-free survival (PFS)	Progression-free survival will be calculated from the date of first treatment to the date of progression or death	2.5 years
Overall survival (OS)	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.	2.5 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (Actual): February 22, 2018

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Liposomal gemcitabine
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: FF10832US101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No