Clinical Trials /

Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors

NCT03690154

Description:

This research study is being done in people with advanced-stage solid tumor cancer. Advanced stage solid tumor cancer is a cancer that forms an abnormal mass of tissue that usually does not contain cysts or liquid areas. Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors include lung cancer, breast cancer, prostate cancer, kidney cancer, colorectal cancer, melanoma and sarcoma. The purpose of this research study is to evaluate the safety of the investigational study drug, FN-1501, at different dose levels. FN-1501 has not previously been given to human subjects. It is intended for the treatment in this study of patients with advanced solid tumor cancers. This study will determine the effects, good and/or bad, on patients' cancer. The main objective of this study is to define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of FN-1501. The MTD is the highest dose a person can take without having bad side effects, and the RP2D will be the dose of FN-1501 used in future studies.

Related Conditions:
  • Acute Myeloid Leukemia
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1, Multi-center, Open-label, Single-arm, Dose-escalation, Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors or Relapsed/Refractory Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: FN-1501-UP1
  • NCT ID: NCT03690154

Conditions

  • Advanced Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
FN-1501FN-1501

Purpose

This research study is being done in people with advanced-stage solid tumor cancer. Advanced stage solid tumor cancer is a cancer that forms an abnormal mass of tissue that usually does not contain cysts or liquid areas. Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors include lung cancer, breast cancer, prostate cancer, kidney cancer, colorectal cancer, melanoma and sarcoma. The purpose of this research study is to evaluate the safety of the investigational study drug, FN-1501, at different dose levels. FN-1501 has not previously been given to human subjects. It is intended for the treatment in this study of patients with advanced solid tumor cancers. This study will determine the effects, good and/or bad, on patients' cancer. The main objective of this study is to define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of FN-1501. The MTD is the highest dose a person can take without having bad side effects, and the RP2D will be the dose of FN-1501 used in future studies.

Detailed Description

      This is a phase 1, first-in-human, open-label, multicenter, dose escalation study.

      Dose escalation will follow the traditional 3+3 design. Patients will be screened for
      eligibility for up to 28 days prior to entry into the study. The starting dose will be 2.5
      mg/day (once daily). The period for DLT assessment is 21 days from the first dose of FN-1501.
      Evaluation of a cohort of at least three (3) patients completing DLT assessment at any given
      dose level is required prior to determining the next dose level and dose regimen for the
      subsequent cohort.

      After the first patient in the cohort receives the Cycle 1, Day 1 dose, subsequent patients
      in that cohort will not be dosed until the first patient has been evaluated for at least 48
      hours to exclude unexpected acute toxicity. The continuous safety evaluation will be
      performed by investigators, the medical monitor, and the sponsor. A Safety Monitoring
      Committee (SMC) will determine dose levels to be administered and dose regimen during dose
      escalation based on the data available from the previous dose levels. If an MTD is not
      identified due to paucity of DLTs, the RP2D will be determined based on pharmacokinetics,
      safety, tolerability, and preliminary efficacy.

      If a patient wishes to continuously receive study treatment on completion of Cycle 1, the
      patient can continue study treatment in 21-day Cycle 2 and subsequent cycles (same as Cycle
      2, all of 21 days' duration), defined as administration of 3 times per week for 2 weeks
      followed by one week off, at the discretion of the investigator.

      The primary endpoint of this study is to determine the recommended phase 2 dose (RP2D) of
      FN-1501 based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
FN-1501Experimental
  • FN-1501

Eligibility Criteria

        Inclusion Criteria:

          -  Male and female 18 years old and above

          -  Able to understand and sign informed consent form

          -  Patients with histologically or cytologically confirmed advanced solid tumors who have
             relapsed or refractory disease or relapsed/refractory AML for which no standard
             therapies expected to produce clinical benefit to the patient are available

          -  Patients with diagnosed solid tumors must have at least one lesion that is measurable
             per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria

          -  Patients with relapsed or refractory AML must be diagnosed with AML based on World
             Health Organization (WHO) criteria (≥ 20% blasts in bone marrow). Patients with acute
             promyelocytic leukemia are excluded

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

          -  Have discontinued all previous cancer therapies for at least 21 days or 5 half-lives
             prior to study treatment, whichever is shorter, and recovered from the acute adverse
             effects of therapy

          -  Expected to survive at least 2 to 3 months

          -  LVEF ≥ 50% and QTc interval < 450 ms

          -  Women shall meet either of the following conditions before enrollment

          -  Infertile, defined as having a bilateral oophorectomy (ovariectomy), or a bilateral
             tubal ligation, or being post-menopausal for at least 1 year.

          -  For those of childbearing potential, they should have a negative serum pregnancy test
             during screening, agree to refrain from lactation, and use effective contraception
             such as hormonal methods associated with inhibition of ovulation, condom,
             intra-uterine device, surgical sterilization (including partner's vasectomy) or sexual
             abstinence during the study and 30 days after the last administration of study drug.

          -  Men who are engaging or plan to engage in sexual activity with a female of
             childbearing potential must either have a prior vasectomy or agree to use effective
             contraception such as condoms, sexual abstinence and appropriate methods taken by
             their partner(s) during the study and 90 days after the last dose.

          -  Patients must have adequate organ functions as indicated by the following screening
             laboratory values:

          -  Serum total bilirubin ≤ 1.5 × upper limit normal (ULN) (Serum total bilirubin can be ≤
             3.0 × ULN if patients have hemolysis or congenital hemolytic diseases)

          -  Creatinine < 1.5 × ULN or estimated creatinine clearance ≥ 50 mL/min

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or

               -  5 X ULN for patient with liver metastases

          -  Absolute neutrophil count (ANC) ≥ 1.5×10^9/L

          -  Platelets ≥ 100×10^9/L

          -  Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (Note: Criteria must be met without a transfusion
             within 2 weeks of obtaining the sample) Note: Laboratory requirements for complete
             blood counts (hemoglobin, ANC, and platelets) do not apply to AML patients

        Exclusion Criteria:

          -  Participation in another therapeutic clinical trial within 3 weeks of enrollment

          -  A previous toxicity-related reaction towards cancer therapy have not recovered within
             2 weeks of enrollment (>Grade 2 National Cancer Institute-Common Terminology Criteria
             for Adverse Events (NCI CTCAE) Version 4.03)

          -  Having received a major surgical operation within 4 weeks of enrollment or not yet
             completely recovered from a previous operation

          -  Any serious or uncontrollable systemic disease, including but not limited to:
             Hypertension (after treatment, systolic blood pressure (SBP) > 180 mmHg and/or
             diastolic blood pressure (DBP) > 100 mmHg) and active hemorrhagic disorders; patients
             who are determined by investigators as otherwise not suitable for participation in
             this study.Note: Patients that in the judgment of the investigator have clinical signs
             of disease progression during the screening period (i.e.: febrile neutropenia, ascites
             requiring drainage, hospitalization due to worsening underlying disease, etc.) will
             not be eligible for participation.

          -  Active known infection, including hepatitis B, hepatitis C, and human immunodeficiency
             virus

          -  Primary central nervous system (CNS) tumor or CNS metastases, as indicated by clinical
             symptoms, cerebral edema, and/or progressive growth (patients with a history of CNS
             metastases or cord compression are allowable if they have been definitively treated
             and have been clinically stable for at least 3 months, and off steroids or
             anticonvulsants ≥ 2 weeks before first dose of study drug)

          -  Serious kidney injury, requiring dialysis

          -  Serious liver injury, and advanced liver diseases of Child-Pugh class B and C

          -  On medications that are strong cytochrome P450(CYP)3A inhibitors or inducers unless
             patients are willing and able to change to use of an equivalent medication that is not
             a strong CYP3A inhibitor or inducer

          -  Cardiac function and disease history which meets one or more of the following
             conditions:

          -  Any risk which may increase QTc interval prolongation, such as hypokalemia, hereditary
             long QT syndrome and taking drugs that can prolong QT interval

          -  Acute myocardial infarction ≤ 6 months prior to Day 1

          -  Clinically significant arrhythmia ≤ 6 months prior to Day 1

          -  Congestive heart failure ≥ Grade 3 by New York Heart Association (NYHA) ≤ 6 months
             prior to Day 1

          -  Cerebral vascular accident (CVA) ≤ 6 months prior to Day 1

          -  Are pregnant or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03
Time Frame:From first dose until 30 days after the last dose.
Safety Issue:
Description:The recommended phase 2 dose (RP2D) of FN-1501 will be determined based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.

Secondary Outcome Measures

Measure:Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC0-last)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Area under concentration-time curve from 0 to 24 hours (AUC(0-24))
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Area under the plasma concentration time curve from zero to infinity (AUC0-∞)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Maximum observed plasma concentration (Cmax)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Time to maximum observed plasma concentration (tmax)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Terminal half-life (t1/2)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Clearance (CL)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Apparent volume of distribution (Vd)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Measurement of anti-tumor activity of FN-1501 according to RECIST version 1.1 (solid tumor)
Time Frame:During the first year.
Safety Issue:
Description:
Measure:Measurement of anti-tumor activity of FN-1501 including but not limited to CT/MRI images
Time Frame:During the first year.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Shanghai Fosun Pharmaceutical Development Co, Ltd.

Last Updated

February 7, 2020