Pharmacodynamics (PD) and Pharmacokinetics (PK) Study of EP-100 in Advanced Solid Tumors

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

This study is being done to:

• Test the safety of EP-100 and see what effect (good and bad) it has on the patient and their cancer;
• Find the highest dose of EP-100 that can be given without causing bad side effects;
• Examine how much EP-100 is in the blood at certain times after it is given and how quickly the body gets rid of it;
• Observe whether there is any effect of EP-100 on the size and activity of cancer in the patient's body.

Inclusion Criteria:

• 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 approved therapy
• 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 study-related procedures.
• 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 institutional normal.
• 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

Exclusion Criteria:

• 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 therapy
• 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 therapy.
• Patients who have potentially life-threatening disease (hypercalcemia, spinal cord compression) whose disease may acutely progress if EP-100 administration causes a flare reaction.
• 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.