Clinical trial NCT02262910: Study of ES414 in Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 1 Study of ES414 in Patients Wtih Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: metastatic castration-resistant prostate cancer
CRPC
Lead sponsor: Aptevo Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-10-13
Enrollment: 35
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose of ES414
timeFrame: during first 28 days of treatment
Secondary outcomes:
measure: Safety Profile of ES414
timeFrame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
measure: Maximum Serum Drug Concentration (Cmax)
timeFrame: Pre- and post-infusion at least weekly during first 28-day cycle, and on Days 1 and 15 of subsequent cycles for an expected duration of 6 months, and for up to 8 weeks following last treatment
measure: Area under the concentration versus time curve (AUC)
timeFrame: Pre- and post-infusion at least weekly during first 28-day cycle, and on Days 1 and 15 of subsequent cycles for an expected duration of 6 months, and for up to 8 weeks following last treatment
measure: Elimination half-life (T1/2)
timeFrame: Pre- and post-infusion at least weekly during first 28-day cycle, and on Days 1 and 15 of subsequent cycles for an expected duration of 6 months, and for up to 8 weeks following last treatment
measure: Immune-Related Response Criteria (irRC)
timeFrame: Baseline and 6 months
measure: Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: Baseline and 6 months
measure: Pharmacodynamics of ES414
timeFrame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
measure: PSA Response
timeFrame: Baseline and 6 months
measure: Circulating Tumor Cells
timeFrame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
measure: Immunogenicity of ES414
timeFrame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 8 weeks following last treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California
state: California
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Temple
country: United States
facility: Central Texas Veterans Health Care System
state: Texas
city: Seattle
country: United States
facility: University of Washington/Seattle Cancer Care Alliance
state: Washington
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital Sydney
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
affiliation: Aptevo Therapeutics
name: Scott C Stromatt, MD
role: STUDY_DIRECTOR
References: