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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumors, Advanced Solid Tumors

Intervention / Treatment
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* Drug: EP-100


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: EP-100|as a single agent administered intravenously twice weekly x 3 with 1 week off (total 28 days)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of EP-100 |  | weekly | 
| To establish the dose of EP-100 recommended for future phase II protocols |  | weekly |