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A Phase 1 Dose-escalation Study of FF-10832 for Treatment of Solid Tumors Including Biliary Tract Cancer

Phase 1
Active, not recruiting
Conditions
Biliary Tract Cancer
Advanced Solid Tumors
Interventions
Drug: FF-10832 Gemcitabine Liposome Injection
Registration Number
NCT03440450
Lead Sponsor
Fujifilm Pharmaceuticals U.S.A., Inc.
Brief Summary

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 including biliary tract cancer

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 18 patients in a 21 day cycle.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
90
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)

  4. Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment

  5. 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

  6. Pregnant or breast-feeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 4: Treatment at 8 mg/m2FF-10832 Gemcitabine Liposome InjectionFF-10832 Gemcitabine Liposome Injection, 8 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
Cohort 1: Treatment at 1.2 mg/m2FF-10832 Gemcitabine Liposome InjectionFF-10832 Gemcitabine Liposome Injection, 1.2 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
Cohort 3: Treatment at 4.8 mg/m2FF-10832 Gemcitabine Liposome InjectionFF-10832 Gemcitabine Liposome Injection, 4.8 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
Expansion Cohort: Treatment at Recommended Phase 2 Dose (RP2D)FF-10832 Gemcitabine Liposome InjectionFor patients with biliary tract cancer: FF-10832 Gemcitabine Liposome Injection, RP2D administered intravenously (IV) on Day 1 of each 21-day cycle
Cohort 2: Treatment at 2.4 mg/m2FF-10832 Gemcitabine Liposome InjectionFF-10832 Gemcitabine Liposome Injection, 2.4 mg/m2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle
Primary Outcome Measures
NameTimeMethod
Identify dose-limiting toxicities (DLT) of FF-108322.5 years

DLT is defined as any adverse event at least possibly related to FF-10832, and meeting specified DLT criteria

Determine maximun tolerated dose (MTD) of FF-108322.5 years

MTD is defined as the next lower dose of a cohort where patients experienced a DLT

Determine incidence of Treatment Emergent Adverse Events (TEAE)2.5 years

Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)2.5 years

Progression-free survival will be calculated from the date of first treatment to the date of progression or death

Disease Assessment by CT or MRI scan for solid tumors2.5 years

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)

Disease Assessment by CT or MRI + PET scan for pancreatic cancer2.5 years

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.

Duration of Response2.5 years

Duration of Response is calculated from the date of first response to the date of progression or death

Overall survival (OS)2.5 years

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.

Duration of Stable Disease2.5 years

Duration of Stable Disease is the length of time from the start of the treatment until the criteria for progression are met

Time to progression (TTP)2.5 years

Time to progression is calculated from the date of first treatment to the date of first progression

Trial Locations

Locations (6)

Honor Health Research Institute

🇺🇸

Scottsdale, Arizona, United States

University of Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

Hoag Memorial Hospital Comprehensive Cancer Center

🇺🇸

Newport Beach, California, United States

Sarah Cannon Research Institute

🇺🇸

Nashville, Tennessee, United States

MD Anderson Cancer Research Center

🇺🇸

Houston, Texas, United States

Virginia Mason Medical Center

🇺🇸

Seattle, Washington, United States

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