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A Multicenter, Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors

Phase 1/Phase 2
18 Years
Not Enrolling
Advanced Solid Tumors

Thank you

Trial Information

A Multicenter, Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors

JI-101 is a compound being developed for the treatment of patients with solid tumors;
specifically patients for which no approved therapy or standard of care is available or have
solid tumors and have failed standard of care therapy. JI-101 is an inhibitor of vascular
endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta
(PDGFRβ), and EphB4 receptor, each of which plays an important role in driving
vascularization (angiogenesis and vasculogenesis) during normal development and
tumorigenesis. JI-101 inhibits the growth of new blood vessels, which in turn, may slow or
prevent the growth of tumors. The purpose of this open label study is to treat patients
with advanced solid tumors, with increasing doses of JI-101, thereby providing information
about the maximum tolerated dose (MTD). The study will also examine safety, tolerability,
pharmacokinetics, pharmacodynamics, and may evaluate the effects of the drug on tumor
metabolism. During this dose-escalation study, at least two patients will be dosed at each
dose level (cohort). The patients must complete 21 days of dosing and safety results will
be reviewed prior to any patients being assigned the next higher dose level. A continuous
reassessment method will be utilized to escalate JI-101 doses between cohorts. Doses will
be increased, with an anticipated high dose of 800mg per day. If the MTD is not reached, an
optimal biologic dose (OBD) will be determined based on the highest doses that are tolerable
with acceptable efficacy. The cohort at MTD or OBD will be expanded to include up to 30
patients with solid tumors to further explore the safety and tolerability of
orally-administered JI-101.

Inclusion Criteria:

- Be 18 years of age or greater at the time of consent.

- Have solid tumors for which no approved therapy or standard of care is available or
have solid tumors and have failed standard-of-care therapy.

- Have life expectancy of greater than 3 months.

- Have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

- Have organ and marrow function as defined below:

- absolute neutrophil count ≥ 1.5 x 10^9 cells/L

- hemoglobin ≥ 9.0 g/dL

- platelets ≥ 75 x 10^9 cells/L

- total bilirubin ≤ 1.5 x upper limit of normal (ULN)

- AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤ 5 x ULN for liver metastases)

- serum creatinine < 1.5 x ULN

- < 500 mg urinary protein/24 hours or dipstick < 2+

- No evidence of preexisting uncontrolled hypertension as documented by two baseline
blood pressure readings taken at least 1 hour apart (the baseline systolic blood
pressure readings must be <140 mm Hg, and the baseline diastolic blood pressure
readings must be <90 mm Hg. Patients whose hypertension is controlled by
antihypertensive therapies are eligible)

- Have no clinically significant disease that poses a risk to the patient and/or would
interfere with study evaluations or procedures.

- Have within normal range cardiac function as measured by twelve-lead
electrocardiogram at Screening.

- Be clinically euthyroid.

- If female, must be postmenopausal (at least 1 year from last menses), or surgically
sterile, or if a female patient of childbearing potential they must agree to use
acceptable methods of birth control, which include local double-barrier contraceptive
methods, such as cervical diaphragm plus spermicide, female condom plus spermicide,
or a non-hormonal intrauterine device (IUD) plus spermicide, or systemic
contraceptive methods, such as oral, injectable, transdermal or implantable hormonal
contraceptives (including hormone-containing IUDs) during the study period, and for
30 days after the last dose of study drug. Female patients of childbearing potential
must have a negative serum pregnancy test within the 3 days before the first study
drug administration. Male patients must be surgically sterile or also agree to use
acceptable methods of birth control with their female partners, and this may include
use of a male condom plus spermicide. If the subject is practicing abstinence at the
time of Screening, he/she must agree to use a double-barrier contraceptive method if
he/she becomes sexually active.

- Be able to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Be pregnant or breastfeeding.

- Have a known history of human immunodeficiency virus (HIV) infection because the
effect of JI-101 on immunosuppression and drug interactions with anti-retroviral
medications is unknown.

- Have participated in an investigational drug/device/biologic study within 30 days (or
within 5 half-lives of the treatment, whichever is longer) before Visit 1 or who are
currently participating in another investigational drug/device/biologic study.
Participation in non-interventional or observational studies is allowed.

- Have a history of cardiac abnormalities including: abnormal and clinically relevant
ECGs; frequent palpitations or syncopal episodes; heart failure; hypokalemia; stroke;
family history of Long QT Syndrome; acute myocardial infarction or ventricular
tachyarrhythmia within the previous 12 months.

- Have used concomitant medications that prolong the QT/QTc interval within 14 days
prior to Day 1.

- Have a history of significant retinopathy or any progressive eye disease that could
lead to severe loss of visual acuity or visual field loss during the study period.

- Have had therapeutic reanticoagulation with heparin or heparin analogs (low molecular
weight heparins) or warfarin within the past 4 weeks. Low dose warfarin (1 to 2
mg/day) is allowed for prophylaxis treatment.

- Have had major surgery, radiotherapy, chemotherapy, or cytokine therapy within 4
weeks of treatment initiation. Patients must have recovered to baseline or grade 1
from any clinically significant adverse event experienced during those prior

- Have gastrointestinal abnormalities including inability to take oral medications,
malabsorption syndromes or other clinically significant GI abnormalities that may
impair the absorption of JI-101 in the opinion of the Investigator.

- Have uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, unstable angina pectoris, or psychiatric illness/social situations
that would pose a risk to patient safety or that would limit compliance with study

- Have any condition that, in the opinion of the Investigator, would interfere with a
patient's ability to perform the required activities of the study or would subject
the patient to undue risk.

- Patients with proteinuria (patients with >2+ protein on urine dipstick) at baseline
should undergo a 24-hour urine collection. Results must demonstrate <500 mg of
protein in 24 hours to allow participation in the study)

- Patients with any of the following contraindications to FDG-PET can participate in
the study if all of the inclusion criteria and none of the exclusion criteria are
met, but these patients are excluded from FDG PET assessments:

o Inability to remain lying down in PET scanner (for PET portion of the study).

- Absence of at least one metastatic lesion greater than or equal to 2 cm on pre-dose
CT (computed tomography) scan or other radiographic imaging as defined by response
evaluation criteria in solid tumors (RECIST) criteria.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of JI-101

Outcome Description:

The primary objective of this study was to determine the maximum tolerated dose (MTD) of JI-101 when administered orally in patients with advanced solid tumors. The MTD was established based on safety data from Cycle 1. Patients who completed 21 days of treatment in Cycle 1 were considered to have completed the study for the determination of MTD. Patients were eligible to continue treatment with JI-101 until they experienced disease progression or unacceptable treatment-related toxicity. Unacceptable treatment-related toxicity was defined as a clinically significant AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and that was attributed to JI 101.

Outcome Time Frame:

28 days (1 cycle)

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

February 2009

Completion Date:

January 2012

Related Keywords:

  • Advanced Solid Tumors
  • solid tumors
  • angiogenesis inhibitor
  • dose escalation
  • maximum tolerated dose
  • JI-101
  • Neoplasms



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