Clinical Trials /

Safety and Pharmacokinetic Study of IT-141 in Monotherapy in Patients With Advanced Cancer

NCT03096340

Description:

IT141 is a novel nanoparticle formulation of SN-38, the active metabolite of irinotecan, and is intended to deliver more drug to the tumor with reduced toxicity on normal tissues. The study is designed to determine the maximum tolerated dose (MTD) of IT-141, and to investigate pharmacokinetic (PK) parameters and possible pharmacodynamics (PD) relationships. Patients will also be monitored for any response to therapy.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Pharmacokinetic Study of IT-141 in Monotherapy in Patients With Advanced Cancer
  • Official Title: A Phase 1 With Expansion Cohort, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Intravenously Infused IT-141 in Subjects With Recurrent or Refractory Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: IT141-001
  • NCT ID: NCT03096340

Conditions

  • Cancer
  • Neoplasms
  • Tumors
  • Refractory Solid Tumors
  • Recurrent Solid Tumors

Interventions

DrugSynonymsArms
IT-141IT-141, 7-ethyl-10-hydroxycamptothecinIT-141

Purpose

IT141 is a novel nanoparticle formulation of SN-38, the active metabolite of irinotecan, and is intended to deliver more drug to the tumor with reduced toxicity on normal tissues. The study is designed to determine the maximum tolerated dose (MTD) of IT-141, and to investigate pharmacokinetic (PK) parameters and possible pharmacodynamics (PD) relationships. Patients will also be monitored for any response to therapy.

Trial Arms

NameTypeDescriptionInterventions
IT-141Experimental
  • IT-141

Eligibility Criteria

        Inclusion Criteria:

          -  Must be 18 years of age or older.

          -  Must be males or non-pregnant females who agree to comply with applicable
             contraceptive requirements of the protocol.

          -  Must have a histologically or cytologically confirmed, incurable malignancy, for which
             further standard treatment is not currently available.

          -  Must have measurable or evaluable disease during the dose escalation phase (measurable
             disease is preferred for the expanded cohort after MTD is reached).

          -  Must have an anticipated survival of at least 12 weeks.

          -  Must be fully informed regarding their illness and the investigational nature of the
             study protocol, and must sign an Institutional Review Board (IRB) approved Informed
             Consent Form (ICF).

          -  Must be ambulatory, with an Eastern Cooperative Oncology Group (ECOG) performance
             score of 0 or 1.

          -  Must have adequate organ function, as defined by the following:

          -  Hematologic: ANC 1.5 x 109/L, Hgb ≥ 9.0 g/dL and platelet count 100 x 109/L (platelet
             count > 75 x 109/L if documented evidence of bone marrow involvement).

          -  Hepatic: Total bilirubin 1.5 x ULN; transaminases ≤ 2.5 x ULN (may be up to 5 x ULN if
             clearly due to liver metastases); prothrombin time (PT) and partial thromboplastin
             time (PTT) < 2 x (ULN).

          -  Renal: Serum creatinine 1.5 x ULN or creatinine clearance 60 mL/min.

          -  Must be on stable doses of any drugs affecting hepatic drug metabolism or renal drug
             excretion (e.g. non-steroidal anti-inflammatory drugs, corticosteroids, barbiturates,
             diphenylhydantoin, narcotic analgesics, probenecid). Such drugs should not be
             initiated less than 30 days prior to Baseline/C1D1 or at any time during study
             participation. Whenever possible, narcotic analgesic doses should be stable within 30
             days prior to study entry and during the first cycle of therapy.

          -  Must be recovered from any reversible side effects of prior therapy (e.g. no major
             surgery, no antineoplastic or experimental therapy, or no significant radiation
             therapy to hematopoietic sites within 4 weeks of Baseline/C1D1, and no nitrosoureas or
             nitrogen mustards within 6 weeks of Baseline/C1D1)

          -  Must understand and be able, willing, and likely to fully comply with study procedures
             and restrictions.

        Exclusion Criteria:

          -  Current or recurrent disease that could affect the action or disposition of IT-141, or
             clinical or laboratory assessments.

          -  Subjects with UGT1A1*28 polymorphisms.

          -  Current or relevant previous history of serious, severe or unstable (acute or
             progressive) physical or psychiatric illness, including any medical disorder that may
             require treatment or make the subject unlikely to fully complete the study, or any
             condition that presents undue risk from the IP or procedures.

          -  Primary brain tumors or known brain metastasis unless clinically stable and on stable
             or reducing doses of steroids.

          -  Frequent vomiting.

          -  Recent history of unintentional weight loss > 10% of current body weight in the past 3
             months.

          -  Ongoing radiation therapy, chemotherapy, or hormonal therapy. Point radiation to a
             site of bone pain will be allowed.

          -  Current (within 1 week of Screening) or regular use of any medication (including
             over-the-counter (OTC), herbal or homeopathic preparations) that could improve or
             worsen the cancer being studied, or could affect the action or disposition of IT-141,
             or its clinical or laboratory assessment; e.g. Coumadin therapy, due to high
             competitive protein binding. Subjects taking ANY supplemental IRON, i.e., therapeutic
             or as part of a multivitamin regimen, are excluded from this study, whether prescribed
             or self-medicated.

          -  Concomitant use of a UGT1A1 inhibitor, such as idinavir, atazanavir and sorafenib,
             throughout the study period.

          -  Known or suspected intolerance or hypersensitivity to IT-141 or any of the stated
             ingredients.

          -  History of alcohol or other substance abuse within the last year.

          -  History of use of another IP within the last 4 weeks prior to enrollment.

          -  Female subjects who are pregnant or lactating, including females with a positive
             pregnancy test at screening.

          -  Previous enrollment in this study, followed by withdrawal for any reason.

          -  Known HIV-positive subjects on combination anti-retroviral therapy due to the
             potential for PK interactions with the study agent.

          -  Evidence of ischemia or myocardial infarction within the past 6 months, or any
             significant abnormality on ECG.

          -  A QTc interval outside of normal. (Normal: < 450 msec for males and < 460 msec for
             females)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of IT-141 administered once every 2 weeks in patients with refractory solid tumors
Time Frame:18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Adverse event profiles according to the Common Toxicity Criteria for Adverse Events (CTCAE, ver. 4.03)
Time Frame:18 months
Safety Issue:
Description:
Measure:Objective response rate based on RECIST
Time Frame:18 months
Safety Issue:
Description:
Measure:Area under the plasma concentration versus time curve (AUC) of SN-38 and SN-38G
Time Frame:18 months
Safety Issue:
Description:
Measure:Maximum plasma concentration (Cmax) of SN-38 and SN-38G
Time Frame:18 months
Safety Issue:
Description:
Measure:Time to Cmax (Tmax) of SN-38 and SN-38G
Time Frame:18 months
Safety Issue:
Description:
Measure:Elimination rate constant of SN-38 and SN-38G
Time Frame:18 months
Safety Issue:
Description:
Measure:Terminal half-life (t1/2) of SN-38 and SN-38G
Time Frame:18 months
Safety Issue:
Description:
Measure:Total plasma clearance (CL) of SN-38 and SN-38G
Time Frame:18 months
Safety Issue:
Description:
Measure:Volume of distribution (Vz) of SN-38 and SN-38G
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Intezyne Technologies, Inc.

Trial Keywords

  • SN-38
  • irinotecan

Last Updated

February 9, 2018