- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03096340
Safety and Pharmacokinetic Study of IT-141 in Monotherapy in Patients With Advanced Cancer
December 18, 2020 updated by: Intezyne Technologies, Inc.
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
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.
Study Overview
Status
Terminated
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75230
- Mary Crowley Cancer Research Centers - Medical City
-
-
Washington
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Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- 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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum tolerated dose of IT-141 administered once every 2 weeks in patients with refractory solid tumors
Time Frame: 18 months
|
18 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Adverse event profiles according to the Common Toxicity Criteria for Adverse Events (CTCAE, ver. 4.03)
Time Frame: 18 months
|
18 months
|
Objective response rate based on RECIST
Time Frame: 18 months
|
18 months
|
Area under the plasma concentration versus time curve (AUC) of SN-38 and SN-38G
Time Frame: 18 months
|
18 months
|
Maximum plasma concentration (Cmax) of SN-38 and SN-38G
Time Frame: 18 months
|
18 months
|
Time to Cmax (Tmax) of SN-38 and SN-38G
Time Frame: 18 months
|
18 months
|
Elimination rate constant of SN-38 and SN-38G
Time Frame: 18 months
|
18 months
|
Terminal half-life (t1/2) of SN-38 and SN-38G
Time Frame: 18 months
|
18 months
|
Total plasma clearance (CL) of SN-38 and SN-38G
Time Frame: 18 months
|
18 months
|
Volume of distribution (Vz) of SN-38 and SN-38G
Time Frame: 18 months
|
18 months
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall Survival
Time Frame: 18 months
|
18 months
|
Disease Control Rate
Time Frame: 2 years
|
2 years
|
Progression-free Survival
Time Frame: 18 months
|
18 months
|
Time to progression
Time Frame: 18 months
|
18 months
|
MRI imaging for biodistribution of IT-141
Time Frame: 18 months
|
18 months
|
Presence of cfDNA
Time Frame: 2 years
|
2 years
|
Presence of exosomes
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Minal Barve, MD, Mary Crowley Cancer Research Centers - Medical City
- Principal Investigator: Kit Wong, MD, Seattle Cancer Care Alliance
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 23, 2017
Primary Completion (Actual)
August 22, 2018
Study Completion (Actual)
November 26, 2019
Study Registration Dates
First Submitted
March 15, 2017
First Submitted That Met QC Criteria
March 24, 2017
First Posted (Actual)
March 30, 2017
Study Record Updates
Last Update Posted (Actual)
December 22, 2020
Last Update Submitted That Met QC Criteria
December 18, 2020
Last Verified
January 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IT141-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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