Study of FF-10502-01 in Patients With Advanced Solid Tumors and Lymphomas

A Phase 1/2a, Dose-escalation Study of FF-10502-01 for the Treatment of Advanced Solid Tumors and Lymphomas

A Phase 1/2a, dose-escalation study of FF-10502-01 in Patients with Advanced Solid Tumors and Lymphomas. A total of up to 9 cohorts will be enrolled in Phase 1 to establish the MTD. Phase 2 will consist of 2 cohorts: Cohort 1 will include subjects with Pancreatic Cancer. Cohort 2 will include subjects with another tumor type enrolled in the Phase 1 dose-escalation phase who have demonstrated Clinical Benefit by Week 16.

Study Overview

• Status: Completed
• Conditions: Solid Tumors; Lymphomas
• Intervention / Treatment: Drug: FF-10502-01

Detailed Description

Subjects will receive doses of FF-10502-01 intravenously (IV) weekly for three weeks, repeated every 28 days (= 1 cycle). Disease assessments, based on computed tomography (CT), magnetic resonance image (MRI), and, for lymphoma, [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans, will be obtained at Week 8 and every 8 weeks thereafter until documented progression of disease (PD). Subjects who demonstrate clinical benefit will be allowed to continue therapy with FF-10502-01 until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and females ≥ 18 years of age
• Histologically or cytologically confirmed advanced or metastatic solid tumor or l lymphoma, that is refractory to standard therapy, relapsed after standard therapy, or for which no standard therapy available that is expected to improve survival by at least three months
• At least 4 weeks beyond the last chemotherapy (or ≥ 5 half-lives for targeted agents, whichever is shorter), radiotherapy, major surgery or experimental treatment and recovered from all acute toxicities (≤ Grade 1)
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Life expectancy of ≥ 3 months
• Adequate hematologic parameters without ongoing transfusional support:
• Hemoglobin (Hb) ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L
• Platelets ≥ 100 x 109 cells/L
• Adequate renal and hepatic function:
• Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance ≥ 60 mL/minute x 1.73 m2 per the Cockcroft-Gault formula
• Total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease
• ALT/AST ≤ 2.5 times ULN, or < 5 times ULN for subjects with liver metastases
• QT interval corrected for rate (QTc) ≤ 480 msec on the electrocardiogram (ECG) obtained at Screening
• Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study and for 28 days after the completion of study treatment.
• Ability to provide written informed consent

Exclusion Criteria:

• 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
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of anti-microbials 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
• Active central nervous system (CNS) malignant disease in subjects with a history of CNS malignancy. Subjects with stable, prior or currently treated brain metastases are allowed.
• Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
• Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment
• 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
• Pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 1.5x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 2.25x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 3.375x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 5x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 7.5x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 11.25x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 16.875x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 1: 25x lowest dose of FF-10502-01; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 2a: FF-10502-01 at MTD in Pancreatic Cancer; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01
Experimental: Phase 2a: FF-10502-01 at MTD in Solid Tumors; FF-10502-01 will be administered intravenously (IV) on Days 1, 8, and 15 of a 28 day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.	Drug: FF-10502-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)	Safety and tolerability assessed by adverse events (AEs), and serious adverse events. (SAEs)	33 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of overall response rates	Determination of overall response rates	Responses assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug (every 28 days=1 cycle).
Determination of duration of response.	duration of response is determined	Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug
Determination of duration of stable disease (SD) as measured from time of 1st evidence of response to time of 1st evidence of progressive disease as measured by CT or MRI.	measurement of stable disease	Assessed at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug
Evaluate progression-free survival (PFS)	measurement of PFS	Responses and survival assessed, at the end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug
Evaluate overall survival (OS)	measurement of OSS	Assessed by telephone call at end of C2 and every 2 cycles thereafter through 6 months following last dose of study drug
Evaluate the mean plasma concentrations of FF-10502-01	measurement of plasma concentrations	Assessed at Cycle 1 Day 1, and Cycle 1 Day 15
Evaluate FF-10502-01 incorporation into whole blood cellular DNA by LC-MS/MS as a pharmacodynamic marker	measurement of cellular DNA	Assessed at Cycle 1 Day 1, Cycle 1 Day , Cycle 1 Day 15, Cycle 1, Day 22, Cycle 2 Day 1, at the end of Cycle 2 and ever 2 cycles thereafter up to 24 weeks.

Collaborators and Investigators

• Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
• Investigators: Principal Investigator: Filip Janku, MD, University of Texas MD Anderson Center; Principal Investigator: Gerald Falchook, MD, Sarah Cannon Research Institute-Denver

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): November 5, 2020
• Study Completion (Actual): November 5, 2020

Study Registration Dates

• First Submitted: January 13, 2016
• First Submitted That Met QC Criteria: January 19, 2016
• First Posted (Estimate): January 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: FF1050201US101

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