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Castration Levels of TestosteronePhase 2NCT04033432

sEphB4-HSA in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

A Phase 2 study testing Recombinant EphB4-HSA Fusion Protein in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Northwestern University at 3 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this phase II, single-arm, open-label, three center study is to evaluate the efficacy, safety, and tolerability of sEphB4-HSA in patients with mCRPC (metastatic castration-resistant prostate cancer). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Recombinant EphB4-HSA Fusion Protein
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
3 sitesUnited States
Study dates
20 Sep 2019to 30 Jun 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have a pathologically confirmed diagnosis of prostate adenocarcinoma
  • Patients must have metastatic (M1) disease as evidenced by soft tissue and/or bony metastases on computed tomography (CT) or magnetic resonance imaging (MRI) scan or technetium bone scan
  • Patients must have castration resistant disease with disease progression despite castrate levels of testosterone (testosterone =< 50 ng/dL)
  • Patients must have received and progressed on at least one second generation androgen receptor (AR) targeted therapy for castration resistant disease irrespective of prior chemotherapy. No more than 3 prior treatment therapies for castration resistant disease (life prolonging) are permitted. Prior therapy can include:
  • Second generation AR targeted therapy (i.e. abiraterone, enzalutamide, or other new antiandrogen [ODM-201, apalutamide])
  • Chemotherapy (docetaxel and/or cabazitaxel)
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  • Documented progressive mCRPC based on at least one of the following criteria:
  • PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL
  • Progression of bi-dimensionally measurable soft tissue or nodal metastasis assessed within one month prior to registration by a CT scan or MRI
  • Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan
  • Serum testosterone < 50 ng/dL. Patients must continue primary androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomy
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Patients must have adequate organ and bone marrow function as defined below within 28 days of registration:
  • Absolute neutrophil count >= 1,000/mcL (within 28 days of registration)
  • Hemoglobin >= 9 g/dL* (within 28 days of registration)
  • Transfusion is allowed as long as patients have not received prior transfusion =< 28 days from registration
  • Bilirubin =< 1.5 x institutional upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert?s syndrome, who can have total bilirubin < 3.0 mg/dL (within 28 days of registration)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN (=< 5 x ULN if liver metastases present) (within 28 days of registration)
  • Serum creatinine =< 2.0 X ULN (upper limit of normal) or creatinine clearance >= 30 mL/minute (using Cockcroft/Gault formula) (within 28 days of registration)
  • Platelet >= 100,000 (within 28 days of registration)
  • Patients must use a condom during treatment and for 3 months after the last dose of study treatment when having sexual intercourse. Female partners of male subjects should also use a highly effective form of contraception if they are of childbearing potential. Subjects should not donate sperm throughout the study and for 3 months following the last dose of treatment
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Who cannot join

  • Patients who have received more than 3 prior treatment therapies (life prolonging) for mCRPC are not eligible
  • Patients who have had radiotherapy =< 14 days prior to entering the study are not eligible
  • Note: Palliative radiation therapy is allowed
  • Patients who have had systemic therapy for prostate cancer =< 21 days or 5-half lives (whichever is shorter) are not eligible
  • Note: Patients can receive a stable dose of bisphosphonates for bone metastases, including zoledronic acid, or denosumab before and during the study as deemed appropriate by the treating physician. Patients must continue androgen deprivation therapy
  • Patients receiving any other investigational agents are not eligible
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  • Patients with small cell carcinoma of the prostate are not eligible
  • Note: Neuroendocrine differentiation is permitted. If there is doubt about this and it is clinically indicated then a biopsy should be obtained to document histological differentiation
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to sEphB4-HSA are not eligible. AND patients who have had prior exposure to compounds of similar chemical or biologic composition to sEphB4-HSA are not eligible
  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure (New York Heart Association class III or IV congestive heart failure)
  • Unstable angina pectoris
  • Serious cardiac arrhythmia
  • Patients with uncontrolled hypertension (defined as systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 95 mmHg) are not eligible
  • Note: Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
  • Patients with electrocardiogram (ECG) with QT interval (corrected QT interval [QTc]) > 480 msec are not eligible
  • Patients with other malignancy that has progressed or has required active systemic treatment in the last 3 years
  • Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or carcinoma in situ or non-muscle invasive bladder cancer are not excluded
  • Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis are not eligible
  • Note: A scan to confirm the absence of brain metastases is not required. Subjects with previously treated brain metastases may participate provided they are stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), without requirement of steroid treatment for at least 4 weeks prior to randomization and with any neurologic symptoms resolved or have returned to baseline of prior treatment for brain metastasis
  • Patients with spinal cord compression are not eligible unless considered to have received definitive treatment for this and evidence of stable disease for 28 days
  • Patients who underwent major surgery =< 14 days of starting study treatment or have not recovered from effects of surgery are not eligible

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: A Phase II Study of sEphB4-HSA in Metastatic Castration-Resistant Prostate Cancer

The purpose of this phase II, single-arm, open-label, three center study is to evaluate the efficacy, safety, and tolerability of sEphB4-HSA in patients with mCRPC (metastatic castration-resistant prostate cancer). The study drug, sEphB4-HAS, is a form of protein that has not been approved for sale by the United States Food and Drug Administration (FDA). The study drug prevents tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the efficacy of recombinant EphB4-HSA fusion protein (sEphB4-HSA) in patients with metastatic castration resistant prostate cancer (mCRPC) as measured by confirmed prostate specific antigen (PSA) response rate.

SECONDARY OBJECTIVES:

  1. The safety and tolerability of sEphB4-HSA in patients with mCRPC according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

II. To assess the time to PSA progression. III. To assess overall response rate in patients with measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone) criteria.

IV. To assess radiological progression free survival (rPFS) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria.

EXPLORATORY OBJECTIVES:

  1. To explore molecular changes associated with EphB4 and ephrinB2 expression in tumor specimens (primary and/or metastatic tissue).

II. To explore association of response with molecular biomarkers including aberrations in the PI3K pathway, MYC and TP53.

III. To assess immune cell infiltration of tumors in biopsies. IV. To assess circulating immune changes associated with treatment.

OUTLINE:

Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for cycles 1-6 and then every 21 days for subsequent cycles. Patients may continue to receive sEphB4-HSA treatment until no longer clinically benefiting (PCWG3), unacceptable toxicity, treatment delay >= 4 weeks, or prohibitive illness/change in patient?s condition, or patient decides to withdraw from study.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 1 year.

Being tested
Recombinant EphB4-HSA Fusion Protein
Medical subject headings
Disease Progression, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Recombinant EphB4-HSA Fusion ProteinBiological

    Also called sEphB4-HSA

    Given IV

Study groups in NCT04033432
Study groupRoleWhat they receive
Treatment (recombinant EphB4-HSA fusion protein)ExperimentalPatients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on day 1. Treatment repeats every 14 days for cycles 1-6 and then every 21 days for subsequent cycles. Patients may continue to receive sEphB4-HSA treatment until no longer clinically benefiting (PCWG3), unacceptable toxicity, treatment delay >= 4 weeks, or prohibitive illness/change in patient?s condition, or patient decides to withdraw from study.
Receives: Biological: Recombinant EphB4-HSA Fusion Protein

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prostate Specific Antigen (PSA) Response Rate

    Assessment of confirmed PSA response rate is the proportion of subjects who received at least 1 dose of the study drug achieving a post-treatment PSA partial response or complete response as defined by PSA response criteria.

    PSA response criteria:

    These definitions are intended to characterize the PSA changes on study for the purpose of reporting of results.

    Complete Response (CR): Undetectable PSA (<0.2 ng/ml) that is confirmed by another PSA level at no less than 4 weeks interval (+/- 3 days).

    Partial Response (PR): Decrease in PSA value by > 50% that is confirmed by another PSA level at no less than 4 weeks interval (+/- 3 days).

    Stabilization(SD): Patients who do not meet the criteria or PR or PD for at least90 days on the study will be considered stable

    Progression (PD): 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by2 ng/ml that is confirmed by another PSA level at no less than 4 weeks interval.

    Measured: Up to 1 year

Secondary outcomes (4)

  1. Incidence of Adverse Events

    Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and reported by the toxicity, severity, and attribution will be recorded for each cycle. All reported adverse event (AE) types will be tabulated by maximum grade using frequencies and percentages. Data on type, timing, frequency and attribution of AEs will also be summarized.

    Measured: Up to 1 year

  2. Time to PSA Progression

    The time to PSA progression will be assessed by calculating the interval from administration of the first dose of drug on cycle 1 day 1 to PSA progression. PSA progression is defined by the criteria. PSA will be assessed every odd cycle. Will use Kaplan Meier methods to estimate the distribution of time to PSA progression. Will estimate the median with two-sided 90% confidence interval (CI).

    Measured: From the start of study treatment to PSA progression, assessed for up to 1 year

  3. Overall Response Rate

    The overall response rate will be the proportion of patients with measurable disease who received at least 1 dose of the study drug and as their best response achieved a partial or complete response (responder). Will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and PCWG3 criteria. Will be reported with two-sided 90% exact binomial CI.

    Measured: Up to 1 year

  4. Time to Radiologic Progression (rPFS)

    The time to rPFS will be assessed by calculating the interval from administration of the first dose of drug on cycle 1 day 1 to the time to radiologic progression by RECIST 1.1 or PCWG3 bone criteria or death from any cause. Radiologic assessment will be every 8 weeks. Will use Kaplan Meier methods to estimate the distribution of rPFS. Will estimate the median with two-sided 90% confidence interval (CI).

    Measured: From the start of study treatment to the time of radiologic progression or death from any cause, assessed for up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2019
  2. Study start20 Sep 2019
  3. Primary completion5 Feb 2021
  4. Study completion30 Jun 2022 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04033432
Sponsor's protocol ID
NU 18U10
Other IDs
NCI-2019-03773, STU00209511, NU 18U10, P30CA060553
Status last verified
Apr 2022
First submitted
24 Jul 2019
Last updated
27 Apr 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • VanderWeele DJ, Kocherginsky M, Munir S, Martone B, Sagar V, Morgans A, Stadler WM, Abdulkadir S, Hussain M. A Phase II Study of sEphB4-HSA in Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer. 2022 Dec;20(6):575-580. doi: 10.1016/j.clgc.2022.08.012. Epub 2022 Sep 7.

    PubMed 36210299

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Recombinant EphB4-HSA Fusion Protein in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Northwestern University at 3 sites in United States.

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 22 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Prostate Specific Antigen (PSA) Response Rate (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04033432, which also lists 1 linked publication.

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 27 Apr 2022.

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