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Study of ES414 in Metastatic Castration-Resistant Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ES414
Sponsored by
Aptevo Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring metastatic castration-resistant prostate cancer, CRPC

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of California
  • Roswell Park Cancer Institute
  • Central Texas Veterans Health Care System
  • University of Washington/Seattle Cancer Care Alliance
  • St. Vincent's Hospital Sydney
  • Monash Medical Centre
  • Peter MacCallum Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ES414

Arm Description

Cohorts 1-3 of the dose escalation stage of the study (Stage 1) will test weekly doses of 0.2 mcg/kg to 2 mcg/kg. Cohorts 4-9 of the dose escalation stage of the study (Stage 1) will test continuous infusion at flat doses of 25 mcg to 300 mcg per day delivered continuously over 24 hours. The maximum tolerated dose from Stage 1 of the study will be further examined in Stage 2. Patients in cohorts 1-3 will receive ES414 weekly via intravenous (IV) infusion during the first three 28-day cycles and then on Day 1 and 15 of each subsequent cycle until disease progression, intolerable toxicity occurs, or the patient withdraws consent. Patients in cohorts 4-9 will receive ES414 as a continuous IV infusion for 6 months until disease progression, intolerable toxicity occurs, or the patient withdraws consent.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose of ES414
Identify the maximum tolerated dose in dose-escalation stage (Stage 1) by assessment of dose-limiting toxicities

Secondary Outcome Measures

Safety Profile of ES414
The safety profile of ES414 will be assessed by monitoring incidence and severity of adverse events
Maximum Serum Drug Concentration (Cmax)
Blood samples will be obtained from all patients for determination of the maximum serum concentration of ES414.
Area under the concentration versus time curve (AUC)
Blood samples will be obtained from all patients for determination of the AUC of ES414.
Elimination half-life (T1/2)
Blood samples will be obtained from all patients for determination of the T1/2 of ES414.
Immune-Related Response Criteria (irRC)
Investigator measurements of target lesions
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Investigator measurements of target lesions
Pharmacodynamics of ES414
Blood samples will be collected from all patients and evaluated by flow cytometry for changes in lymphocytes
PSA Response
Blood samples will be collected from all patients and tested for PSA
Circulating Tumor Cells
Blood samples will be collected from all patients and evaluated for the number of circulating tumor cells
Immunogenicity of ES414
Blood samples will be collected from all patients and tested for antibody formation to ES414.

Full Information

First Posted
September 26, 2014
Last Updated
August 22, 2019
Sponsor
Aptevo Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02262910
Brief Title
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

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
February 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aptevo Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
metastatic castration-resistant prostate cancer, CRPC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ES414
Arm Type
Experimental
Arm Description
Cohorts 1-3 of the dose escalation stage of the study (Stage 1) will test weekly doses of 0.2 mcg/kg to 2 mcg/kg. Cohorts 4-9 of the dose escalation stage of the study (Stage 1) will test continuous infusion at flat doses of 25 mcg to 300 mcg per day delivered continuously over 24 hours. The maximum tolerated dose from Stage 1 of the study will be further examined in Stage 2. Patients in cohorts 1-3 will receive ES414 weekly via intravenous (IV) infusion during the first three 28-day cycles and then on Day 1 and 15 of each subsequent cycle until disease progression, intolerable toxicity occurs, or the patient withdraws consent. Patients in cohorts 4-9 will receive ES414 as a continuous IV infusion for 6 months until disease progression, intolerable toxicity occurs, or the patient withdraws consent.
Intervention Type
Biological
Intervention Name(s)
ES414
Intervention Description
ES414 is a novel humanized bispecific antibody which is designed to treat mCRPC by redirecting T-cell cytotoxicity against prostate cancer cells expressing prostate-specific membrane antigen (PSMA).
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose of ES414
Description
Identify the maximum tolerated dose in dose-escalation stage (Stage 1) by assessment of dose-limiting toxicities
Time Frame
during first 28 days of treatment
Secondary Outcome Measure Information:
Title
Safety Profile of ES414
Description
The safety profile of ES414 will be assessed by monitoring incidence and severity of adverse events
Time Frame
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Title
Maximum Serum Drug Concentration (Cmax)
Description
Blood samples will be obtained from all patients for determination of the maximum serum concentration of ES414.
Time Frame
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
Title
Area under the concentration versus time curve (AUC)
Description
Blood samples will be obtained from all patients for determination of the AUC of ES414.
Time Frame
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
Title
Elimination half-life (T1/2)
Description
Blood samples will be obtained from all patients for determination of the T1/2 of ES414.
Time Frame
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
Title
Immune-Related Response Criteria (irRC)
Description
Investigator measurements of target lesions
Time Frame
Baseline and 6 months
Title
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Description
Investigator measurements of target lesions
Time Frame
Baseline and 6 months
Title
Pharmacodynamics of ES414
Description
Blood samples will be collected from all patients and evaluated by flow cytometry for changes in lymphocytes
Time Frame
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Title
PSA Response
Description
Blood samples will be collected from all patients and tested for PSA
Time Frame
Baseline and 6 months
Title
Circulating Tumor Cells
Description
Blood samples will be collected from all patients and evaluated for the number of circulating tumor cells
Time Frame
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Title
Immunogenicity of ES414
Description
Blood samples will be collected from all patients and tested for antibody formation to ES414.
Time Frame
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 8 weeks following last treatment

10. Eligibility

Sex
Male
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott C Stromatt, MD
Organizational Affiliation
Aptevo Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of California
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Central Texas Veterans Health Care System
City
Temple
State/Province
Texas
ZIP/Postal Code
76504
Country
United States
Facility Name
University of Washington/Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
St. Vincent's Hospital Sydney
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia

12. IPD Sharing Statement

Learn more about this trial

Study of ES414 in Metastatic Castration-Resistant Prostate Cancer

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