A Phase 1, Multi-center, Open-label, Dose-escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of EP-100 Given Intravenously 3 Out of 4 Weeks in Subjects With Advanced Solid Tumors
- Subjects with histologically confirmed solid carcinomas
- Subjects whose tumors over express LHRH receptors in tumor biopsies
- Tumor progression after receiving standard/approved chemotherapy or where there is no
- One or more metastatic tumors measurable on CT scan or evaluable disease
- Karnofsky performance ≥ 70%
- Life expectancy of at least 3 months
- Age greater than or equal to 18 years
- Signed, written informed consent. Consent must be provided prior to performing any
- A negative pregnancy test (if female)
- Acceptable liver function
- Acceptable renal function
- Serum creatinine within normal limits, OR calculated creatinine clearance greater
than or equal to 60 mL/min/1.73 m2 for subjects with creatinine levels above
- Acceptable hematologic status:
- No clinically significant abnormalities
- Acceptable coagulation status:
- For men and women of child-producing potential, the use of effective contraceptive
methods during the study
- New York Heart Association Class III or IV, cardiac disease, myocardial infarction
within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
- Pregnant or nursing women. NOTE: Women of child bearing potential and men must agree
to use adequate contraception (hormonal or barrier method of birth control; or
abstinence) prior to study entry and for the duration of study participation. Should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.
- Treatment with radiation therapy or investigational therapy within 4 weeks prior to
Day 1. Had received chemotherapy prior to study entry equivalent within 3 to 5
half-lives of that chemotherapy agent or 4 weeks prior to study entry (whichever is
shorter) with resolution of any side effects from that previous therapy (6 weeks for
nitrosoureas or Mitomycin C).
- Subjects with active CNS metastases are excluded.
- Subjects with a history of CNS metastases will be eligible if they have been treated
and are stable without symptoms for 4 weeks after completion of treatment, with image
documentation required, and must be off steroids.
- Had major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1
- Had minor surgery within 2 weeks prior to Day 1
- Patients who may benefit from hormonal treatment such as breast cancer patients whose
tumors are hormone receptor positive (ER/PR) and without rapidly progressive visceral
disease or patients with prostate cancer who have not had hormonal manipulation
- Patients who have potentially life-threatening disease (hypercalcemia, spinal cord
compression) whose disease may acutely progress if EP-100 administration causes a
- Unwillingness or inability to comply with procedures required in this protocol
- Known infection with HIV, hepatitis B, or hepatitis C
- Subjects who are susceptible to histamine release (e.g. patients with mastocytosis,
mastocytoma, mast cell leukemia, asthma, hay fever, and other allergic disorders and
disorders that increase mast cell numbers).
- Patients under chronic treatment with corticosteroids.
- Baseline QTc exceeding 450 msec (using the Bazetts formula) and/or patients receiving
class 1A or class III antiarrythmic agents.
- Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
conditions) that could compromise protocol objectives in the opinion of the
investigator and/or the sponsor
- Subjects who are currently receiving any other investigational agent
- Subjects should not be using any LHRH agonists (such as leuprolide [Lupron, Eligard],
buserelin [Suprefact, Suprecor], nafarelin [Synarel], histrelin [Supprelin],
goserelin [Zoladex], deslorelin [Suprelorin, Ovuplant], Triptorelin and others) or
antagonists (such as Abarelix [Plenaxis], Cetrorelix [Cetrotide], Ganirelix [Antagon]
and others) prior to study treatments. If LHRH agonists are being used, a 4-week
washout period is recommended.