Clinical Trials /

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

NCT04033432

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: sEphB4-HSA in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
  • Official Title: A Phase II Study of sEphB4-HSA in Metastatic Castration-Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: NU 18U10
  • SECONDARY ID: NCI-2019-03773
  • SECONDARY ID: STU00209511
  • SECONDARY ID: NU 18U10
  • SECONDARY ID: P30CA060553
  • NCT ID: NCT04033432

Conditions

  • Castration Levels of Testosterone
  • Castration-Resistant Prostate Carcinoma
  • Castration-Resistant Prostate Carcinoma Refractory to Second-Generation Androgen Receptor Axis-Targeted Agents
  • Metastatic Prostate Adenocarcinoma
  • Progressive Disease
  • Prostate Carcinoma Metastatic in the Bone
  • Prostate Carcinoma Metastatic in the Soft Tissue
  • PSA Progression
  • Stage IVB Prostate Cancer AJCC v8
  • Testosterone Less Than 50 ng/dL

Interventions

DrugSynonymsArms
Recombinant EphB4-HSA Fusion ProteinsEphB4-HSATreatment (recombinant EphB4-HSA fusion protein)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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:

      I. 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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • Recombinant EphB4-HSA Fusion Protein

Eligibility Criteria

        Inclusion Criteria:

          -  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)

          -  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

        Exclusion Criteria:

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Prostate specific antigen (PSA) response rate
Time Frame:Up to 1 year
Safety Issue:
Description:Will be evaluated per the Prostate Cancer Working Group 3 (PCWG3) criteria. PSA response rate is defined as 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.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 1 year
Safety Issue:
Description: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.
Measure:Time to PSA progression
Time Frame:From the start of study treatment to PSA progression, assessed for up to 1 year
Safety Issue:
Description: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).
Measure:Overall response rate
Time Frame:Up to 1 year
Safety Issue:
Description: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.
Measure:Time to radiologic progression (rPFS)
Time Frame:From the start of study treatment to the time of radiologic progression or death from any cause, assessed for up to 1 year
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Northwestern University

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