Study of ES414 in Metastatic Castration-Resistant Prostate Cancer



Status:Active, not recruiting
Conditions:Prostate Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any
Updated:12/1/2018
Start Date:January 2015
End Date:December 2020

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A Phase 1 Study of ES414 in Patients Wtih Metastatic Castration-Resistant Prostate Cancer

The study will be conducted in 2 Stages. The primary objective of Stage 1 of the study is to
identify the maximum tolerated dose (MTD) of ES414 administered intravenously to patients
with mCRPC. Secondary objectives are to evaluate the tolerability, pharmacokinetics (PK),
pharmacodynamics (PD), immunogenicity, cytokine response, and clinical activity of ES414.

The primary objective of Stage 2 of the study is to evaluate the clinical activity of ES414
in patients that have or have not received prior chemotherapy. Secondary objectives are to
further characterize the safety profile, PK, PD, and immunogenicity of ES414.

Stage 1 - Dose Escalation: The dose escalation stage of the study will test weekly doses of
0.2 mcg/kg to 300 mcg/kg over 9 dose levels (cohorts). Cohorts 1 to 3 consist of single
patients and Cohorts 4 - 9 will consist of a minimum of 3 patients; an additional 3 patients
may be added to the cohort if adverse events possibly related to ES414 or dose-limiting
toxicities (DLT) occur. The next dose cohort will only enroll after the patient(s) in the
current dose cohort have completed the first cycle of dosing (4 weeks) with no significant
adverse events or DLTs. Six patients will be enrolled at the maximum tolerated dose (MTD) and
this dose will be used for Stage 2.

Stage 2 - Expansion: The continuous intravenous infusion MTD dose regimen will be further
examined in 2 expansion cohorts; the first cohort are patients that have received prior
chemotherapy, such as docetaxel for mCRPC, and the second cohort are those that have not
received prior chemotherapy for mCRPC. Serum samples will be collected for serial PK
assessment for ES414 drug levels and antibody formation. Response will be assessed every 2
months during the first 6 months of treatment and then every 3 months until progression of
mCRPC, intolerable side effects, or withdrawal of consent.

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the prostate. No evidence
of neuroendocrine differentiation or small cell features.

- Surgically or medically castrated, with testosterone ≤ 50 ng/dL (≤ 1.7 nmol/L).

- Progressive prostate cancer by either serum PSA levels, soft tissue or bone disease as
defined by the PCWG2 criteria.

- In Stage 1, patients may or may not have received prior chemotherapy for mCRPC. In
Stage 2, patients will be enrolled into two cohorts based on whether or not they have
received prior chemotherapy for mCRPC. Any prior chemotherapy must have been completed
≥ 4 weeks prior to administration of ES414. Additionally, in countries where
abiraterone or enzalutamide are commercially available, patients in Stage 1 and 2 must
have progressed on abiraterone and/or enzalutamide prior to study entry.

- ECOG ≤ 1

- Life expectancy > 6 months per investigator

- Adequate hematologic, renal, and hepatic parameters

Exclusion Criteria:

- Any chemotherapy, sipuleucel-T, or investigational drug in prior 4 weeks, or
abiraterone or enzalutamide in prior 2 week

- Any radiation therapy in prior 2 weeks

- Any prior therapy targeted against PSMA

- History of seizures

- History of central nervous system metastasis

- History of nephrotic syndrome

- Spot urine total protein:creatinine ratio >1,000 mg/gm

- Planned palliative procedures for alleviation of bone pain

- Active infection requiring treatment with systemic anti-infectives or major surgery in
prior 4 weeks.

- Any prednisone (or equivalent corticosteroids) use within 2 weeks of study entry

- Chronic immunosuppressive therapy

- Known history of HIV, hepatitis B, or hepatitis C infection

- Evidence of severe or uncontrolled systemic diseases

- History of bleeding disorders or thromboembolic events in prior 3 months
We found this trial at
5
sites
666 Elm Street
Buffalo, New York 14263
(716) 845-2300
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
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Darlinghurst, New South Wales 2010
Principal Investigator: Anthony Joshua, MD
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San Francisco, California 94143
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Temple, Texas 76504
Principal Investigator: Juan Posada, MD
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Temple, TX
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