An Open-Label Phase I Dose Escalation Study of Intravenous Infusion of Tetra-O-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects With Refractory Malignant Tumors
- Male or female subjects ≥ 18 years of age.
- Subjects with documented evidence of cancer with clinically evaluable disease. Cancer
can be recurrent after primary treatment with surgery, radiation therapy, and/or
chemotherapy and may include those patients for whom no standard or curative therapy
- Measurable tumor by imaging (computed tomography [CT] per Response Evaluation
Criteria in Solid Tumors [RECIST] criteria).
- Life expectancy of at least 3 months in the Investigator's opinion.
- Negative pregnancy test, if in women of childbearing potential, within one week of
- Subjects who have provided written informed consent to participate in the study.
- ECOG performance status of 0, 1, or 2.
- Absolute neutrophil ≥ 1500 cells/µL, hemoglobin ≥ 9 gm/dl, platelets ≥ 100,000/µL,
ALT/AST ≤ 3 x ULN (upper limit of the normal range) unless involved with tumor then <
5 x ULN, bilirubin ≤ 1.5 x ULN, and creatinine ≤ 1.5 x ULN.
- Women who are pregnant or breast-feeding (women of child-bearing potential must have
a negative serum pregnancy test within one week of entering the study.)
- Women of child-bearing potential who are unwilling to use two medically acceptable
forms of contraception during the course of the study (surgical sterilization,
approved hormonal contraceptives, or barrier method with spermicide).
- Treatment with a prior investigational agent within 28 days of entering the study.
- Subjects unable to comply with the study requirements.
- Subjects with a known sensitivity to any of the study medication components.
- Prior chemotherapy, radiation therapy, or surgery for the primary tumor within 28
days of dosing and/or has not recovered from prior therapy toxicities - with the
exception of non-experimental chronic hormone therapy for currently progressive
metastatic prostate cancer. However, local radiation to a site of symptomatic disease
will be acceptable if it has been completed at least 14 days prior to study drug
initiation and subjects have recovered from all treatment-related side effects.
- Subjects exhibiting any of the following: a marked baseline prolongation of QT/QTc
interval (repeated demonstration of a calculated QTc interval > 450), a history of
additional risk factors for torsades de pointes (TdP) (e.g., heart failure,
hypokalemia, family history of long QT syndrome), and subjects unable or unwilling to
refrain from using medications that are known to prolong the QT/QTc ratio during the
course of the study.