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

NCT04033432 | Unknown Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 18U10NCI-2019-03773STU00209511P30CA060553
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief 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). 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.

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

Outcome Measures

Primary Outcomes (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.

  Up to 1 year

Secondary Outcomes (4)

• Incidence of Adverse Events

  Up to 1 year

• Time to PSA Progression

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

• Overall Response Rate

  Up to 1 year

• Time to Radiologic Progression (rPFS)

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

Other Outcomes (3)

• Changes in EphB4 and ephrinB2 Expression

  Baseline up to 1 year

• Circulating Tumor-derived Deoxyribonucleic Acid (ctDNA) Analysis of PI3K Pathway, MYC or TP53

  Up to 1 year

• Immune Infiltrate Characterization in Tumor Specimen

  Up to 1 year

Study Arms (1)

Treatment (recombinant EphB4-HSA fusion protein)

EXPERIMENTAL

Patients 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.

Biological: Recombinant EphB4-HSA Fusion Protein

Interventions

Recombinant EphB4-HSA Fusion Protein BIOLOGICAL

Given IV

Also known as: sEphB4-HSA

Treatment (recombinant EphB4-HSA fusion protein)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• Vasgene Therapeutics, Inc: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (3)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• 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.

  PMID: 36210299 DERIVED

MeSH Terms

Conditions

Disease Progression; Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Maha Hussain, MD
• Organization: Northwestern University

mhussain@northwestern.edu

312-908-5487

Study Officials

• Maha H Hussain, M.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: July 26, 2019
• Study Start: September 20, 2019
• Primary Completion: February 5, 2021
• Study Completion: June 30, 2022
• Last Updated: April 27, 2022
• Results First Posted: April 27, 2022

Record last verified: 2022-04

Locations

US (3)