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Trial record 1 of 1 for:    IT-141
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Safety and Pharmacokinetic Study of IT-141 in Monotherapy in Patients With Advanced Cancer

This study is currently recruiting participants.
Verified March 2017 by Intezyne Technologies, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03096340
First Posted: March 30, 2017
Last Update Posted: March 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Intezyne Technologies, Inc.
  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.

Condition Intervention Phase
Cancer Neoplasms Tumors Refractory Solid Tumors Recurrent Solid Tumors Drug: IT-141 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Intezyne Technologies, Inc.:

Primary Outcome Measures:
  • Maximum tolerated dose of IT-141 administered once every 2 weeks in patients with refractory solid tumors [ Time Frame: 18 months ]

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

Other Outcome Measures:
  • Overall Survival [ Time Frame: 18 months ]
  • Progression-free Survival [ Time Frame: 18 months ]
  • Time to progression [ Time Frame: 18 months ]
  • Disease Control Rate [ Time Frame: 2 years ]
  • MRI imaging for biodistribution of IT-141 [ Time Frame: 18 months ]
  • Presence of cfDNA [ Time Frame: 2 years ]
  • Presence of exosomes [ Time Frame: 2 years ]

Estimated Enrollment: 45
Actual Study Start Date: March 23, 2017
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IT-141 Drug: IT-141
Escalating doses administered in mg/m2, IV (in the vein) on days 1 and 15 of each 28 day cycle until progression or unacceptable toxicity develops.
Other Name: IT-141, 7-ethyl-10-hydroxycamptothecin

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03096340


Contacts
Contact: Carolyn M Paradise, MD 914-844-4465 carolyn.paradise@intezyne.com
Contact: Kevin N Sill, PhD 813-910-2120 kevin.sill@intezyne.com

Locations
United States, Texas
Mary Crowley Cancer Research Centers - Medical City Recruiting
Dallas, Texas, United States, 75230
Contact: Jessica Bondurant    972-566-3065    jbondurant@marycrowley.org   
Principal Investigator: John J Nemunaitis, MD         
Sub-Investigator: Minal Barve, MD         
Sub-Investigator: James P Pak, MD, DABR         
Sub-Investigator: Jairo R Olivares, MD         
Sub-Investigator: James F Strauss, MD         
Sub-Investigator: Reva E Schneider, MD         
Sub-Investigator: Leah Plato, PA         
Sub-Investigator: Analesa G Lyles, PA         
Sponsors and Collaborators
Intezyne Technologies, Inc.
Investigators
Principal Investigator: John J Nemunaitis, MD Mary Crowley Cancer Research Centers - Medical City
  More Information

Publications:
Responsible Party: Intezyne Technologies, Inc.
ClinicalTrials.gov Identifier: NCT03096340     History of Changes
Other Study ID Numbers: IT141-001
First Submitted: March 15, 2017
First Posted: March 30, 2017
Last Update Posted: March 31, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Intezyne Technologies, Inc.:
SN-38
irinotecan

Additional relevant MeSH terms:
Neoplasms
10-hydroxycamptothecin
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action