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.
- 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
- 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
- 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
- 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
- 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