Prostate CancerPhase 1NCT02262910
Study of ES414 in Metastatic Castration-Resistant Prostate Cancer
A Phase 1 study testing ES414 in people with Prostate Cancer, run by Aptevo Therapeutics at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- ES414
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jan 2015to 18 Feb 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States4 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of California
San Francisco, California, 94143
University of Washington/Seattle Cancer Care Alliance
Seattle, Washington, 98109
Central Texas Veterans Health Care System
Temple, Texas, 76504
Australia3 sites
Monash Medical Centre
Clayton, Victoria, 3168
St. Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
Peter MacCallum Cancer Centre
East Melbourne, Victoria, 3002
About this study
Official title: 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.
Read the 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.
- Conditions
- Prostate Cancer
- Being tested
- ES414
- Keywords
- metastatic castration-resistant prostate cancer, CRPC
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ES414Biological
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).
| Study group | Role | What they receive |
|---|---|---|
| ES414 | Experimental | 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. Receives: Biological: ES414 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of ES414
Identify the maximum tolerated dose in dose-escalation stage (Stage 1) by assessment of dose-limiting toxicities
Measured: during first 28 days of treatment
Secondary outcomes (10)
Safety Profile of ES414
The safety profile of ES414 will be assessed by monitoring incidence and severity of adverse events
Measured: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Maximum Serum Drug Concentration (Cmax)
Blood samples will be obtained from all patients for determination of the maximum serum concentration of ES414.
Measured: 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
Area under the concentration versus time curve (AUC)
Blood samples will be obtained from all patients for determination of the AUC of ES414.
Measured: 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
Elimination half-life (T1/2)
Blood samples will be obtained from all patients for determination of the T1/2 of ES414.
Measured: 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
Immune-Related Response Criteria (irRC)
Investigator measurements of target lesions
Measured: Baseline and 6 months
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Investigator measurements of target lesions
Measured: Baseline and 6 months
Pharmacodynamics of ES414
Blood samples will be collected from all patients and evaluated by flow cytometry for changes in lymphocytes
Measured: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
PSA Response
Blood samples will be collected from all patients and tested for PSA
Measured: Baseline and 6 months
Circulating Tumor Cells
Blood samples will be collected from all patients and evaluated for the number of circulating tumor cells
Measured: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Immunogenicity of ES414
Blood samples will be collected from all patients and tested for antibody formation to ES414.
Measured: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 8 weeks following last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2014 (estimated)
- Study startJan 2015
- Primary completionDec 2018
- Study completion18 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aptevo Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott C Stromatt, MD, Study director, Aptevo Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02262910
- Sponsor's protocol ID
- 401
- Status last verified
- Aug 2019
- First submitted
- 26 Sep 2014
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of ES414 in Patients Wtih Metastatic Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02262910
- Acronym / sponsor ID
- 401
- Conditions
- Prostate Cancer
- Keywords
- metastatic castration-resistant prostate cancer, CRPC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Aptevo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jan 2015
- Primary completion
- Dec 2018 (actual)
- Study completion
- 18 Feb 2019 (actual)
- First posted
- 13 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ES414 | Experimental | Biological: ES414Cohorts 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. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ES414ES414 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). | Biological | ES414 |
Primary outcome
Maximum Tolerated Dose of ES414
Time frame: during first 28 days of treatment
Identify the maximum tolerated dose in dose-escalation stage (Stage 1) by assessment of dose-limiting toxicities
10 secondary outcomes
Safety Profile of ES414
Time frame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Maximum Serum Drug Concentration (Cmax)
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
Area under the concentration versus time curve (AUC)
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
Elimination half-life (T1/2)
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
Immune-Related Response Criteria (irRC)
Time frame: Baseline and 6 months
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time frame: Baseline and 6 months
Pharmacodynamics of ES414
Time frame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
PSA Response
Time frame: Baseline and 6 months
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
Immunogenicity of 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott C Stromatt, MD study director
Aptevo Therapeutics
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ES414 in people with Prostate Cancer, run by Aptevo Therapeutics at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose of ES414 (time frame: during first 28 days of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.