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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: FF-10832 Gemcitabine Liposome Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age 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 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 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 Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1 Life expectancy of ≥ 3 months Ability to provide written informed consent Exclusion Criteria: Patients who have not received standard/approved therapies expected to improve survival by at least 3 months Prior hypersensitivity to gemcitabine 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open label, dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Treatment at 1.2 mg/m2<br>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<br>* FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes<br>* Other names: FF-10832;|
| Experimental: Cohort 2: Treatment at 2.4 mg/m2<br>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<br>* FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes<br>* Other names: FF-10832;|
| Experimental: Cohort 3: Treatment at 4.8 mg/m2<br>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<br>* FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes<br>* Other names: FF-10832;|
| Experimental: Cohort 4: Treatment at 8 mg/m2<br>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<br>* FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes<br>* Other names: FF-10832;|
| Experimental: Expansion Cohort: Treatment at Recommended Phase 2 Dose (RP2D)<br>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<br>* FF-10832 to be diluted in dextrose 5% in water (D5W) and intravenously infused at a continuous rate over 30 to 120 minutes<br>* Other names: FF-10832;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liposomal gemcitabine