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Infiltrating Bladder Urothelial CarcinomaPhase 1NCT02767921

sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

A Phase 1 study testing Cytology Specimen Collection Procedure, Laboratory Biomarker Analysis and Radical Cystectomy in people with Infiltrating Bladder Urothelial Carcinoma and Recurrent Bladder Carcinoma, run by University of Southern California at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This pilot clinical trial studies the side effects of recombinant EphB4-HSA fusion protein before surgery in treating patients with transitional cell carcinoma of the bladder, prostate cancer, or kidney cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cytology Specimen Collection Procedure, Laboratory Biomarker Analysis and Radical Cystectomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
2 Aug 2016to 15 Nov 2021
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
  • NOTE: HIPAA authorization may be included in the informed consent or obtained separately
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 14 days prior to being registered for protocol therapy
  • Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation
  • Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy
  • NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
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  • Females must not be breastfeeding
  • Cohort A - T2, Transitional cell carcinoma (TCC) muscle invasive bladder cancer, (patients who are cisplatin ineligible, decline neoadjuvant and/or ineligible for neoadjuvant chemotherapy); must have histological proof of T2, muscle-invasive transitional cell carcinoma of the bladder with no evidence of metastatic; patient with any degree of fixation of the pelvic sidewall are not eligible
  • Cohort B - Prostate cancer (Gleason 7 or less); must have histological proof of Gleason =< 7 with no evidence of metastatic disease (patient with any degree of extra-prostatic capsule extension are not eligible
  • Cohort C - Renal cell carcinoma (> pT1b); must have radiologic suspicion or histological proof of clear cell renal cell carcinoma >= 4 cm with no evidence of metastatic disease; patient with any degree of tumor extension into the renal vein are not eligible; patients must be candidates for contrast-enhanced ultrasound (CEUS) imaging and agree to undergo this additional imaging technique
  • Patients must be willing to undergo a biopsy of the cancerous tissue if one was not taken within the previous year, prior to drug initiation if tumor block is not available; biopsy must be done within 14 days of first planned drug dose
  • Patients must be willing to undergo a radiologic scan (computed tomography [CT] or magnetic resonance imaging [MRI], depending on organ involved) after last drug dose and prior to minimally-invasive surgery
  • Eligible for:
  • Cohort A: Robot-assisted radical cystectomy (RARC) as per the attending urologist
  • Cohort B: Robot-assisted radical Nephrectomy (RARN)/robot-assisted partial nephrectomy (RAPN) as per the attending urologist
  • Cohort C: RAPN as per the attending urologist
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancers for which the patient has been disease-free for at least 5 years
  • No treatment with any investigational agent within 30 days prior to being registered for protocol therapy
  • No prior systemic chemotherapy for transitional cell carcinoma of the bladder (prior intravesical therapy is allowed); any other prior chemotherapy must have been completed > 5 years prior to initiation of therapy
  • Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder
  • NOTE: No radiation therapy within 28 days prior to being registered for protocol therapy; laboratory values must be obtained within 14 days prior to being registered for protocol therapy
  • Total bilirubin < 2.0 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 X ULN
  • Alanine aminotransferase (ALT) =< 2.5 X ULN
  • Serum Creatinine < 2.5 X ULN
  • Absolute neutrophil count (ANC) > 1.5 X K/mm^3
  • Platelets > 100 K/mm^3
  • International normalized ratio (INR) =< 1.2
  • There are currently no known concomitant medications that must be discontinued prior to administration of registration on study and for the duration of sEphB4-HSA
  • No clinically significant infections as judged by the treating investigator
  • No pleural or pericardial effusion of any grade
  • No uncontrolled angina, congestive heart failure or myocardial infraction (MI) within 6 months prior to registration on study
  • No diagnosed arrhythmias
  • No abnormalities on pre-entry electrocardiogram, obtained within 28 days prior to being registered on study
  • No history of diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • No abnormalities no history of diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies) of registration on protocol therapy
  • No abnormalities no history of ongoing or recent (less than or equal to 3 months of registration on protocol therapy) significant gastrointestinal bleeding
  • No ongoing anti-coagulation and/or anti-platelet therapies allowed
  • Patients with diagnosed uncontrolled hypertension (> 150/90 mmHg) are to be excluded
  • Patients with hypertension controlled with medications are allowed
  • No evidence of gross hematuria
  • No evidence of hydronephrosis
  • No evidence of a history of a stroke or myocardial infarction within the last 6 months prior to study enrollment
  • No evidence of a history of wound healing complications prior to study enrollment

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: A Pilot Study of Neoadjuvant sEphB4-HSA in Patients With Genitourinary Cancers

This pilot clinical trial studies the side effects of recombinant EphB4-HSA fusion protein before surgery in treating patients with transitional cell carcinoma of the bladder, prostate cancer, or kidney cancer. Recombinant EphB4-HSA fusion protein may block an enzyme needed for tumor cells to multiply and may also prevent the growth of new blood vessels that bring nutrients to the tumor. Giving recombinant EphB4-HSA fusion protein before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the feasibility of, and adverse events associated with, treatment with soluble ephrin type-B receptor 4 (sEphB4)-human serum albumin (HSA) (recombinant EphB4-HSA fusion protein) prior to minimally invasive robotic surgery in patients with either muscle-invasive transitional cell carcinoma of the bladder; clear cell renal cell carcinoma (4 cm or greater); or prostate cancer Gleason (7 or under).

SECONDARY OBJECTIVES:

  1. To determine tumor response to neoadjuvant sEphB4 as measured by imaging response and pathologic response.

TERTIARY OBJECTIVES:

  1. To evaluate the expression of ephrin type-B receptor 4 (EphB4) and eph-related receptor tyrosine kinase ligand 5 (EphrinB2) in the archival tumor samples and explore potential associations with outcome.

II. To bank specimens for future correlative biomarker studies based on the results of ongoing biomarkers analyses in the phase I of sEphB4-HSA as a single agent.

III. To evaluate changes in deoxyribonucleic acid (DNA) methylation of the surgical specimen after being treated with sEphB4-HSA.

IV. To evaluate the infiltration of immune cells into the tumor due to administering sEphB4-HSA.

  1. To evaluate the impact sEphB4-HSA has on vessel density on the tumor tissue. VI. To assess the applicability of using sEphB4-HSA for treating genitourinary cancers.

VII. To assess the applicability of using contrast-enhanced ultrasound imaging for determining pathological complete response (pCR) rate.

OUTLINE:

Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes once weekly for 3 weeks (3 doses) in the absence of disease progression or unacceptable toxicity. Patients who agree may receive the fourth dose after an additional week as determined by the study medical oncologist. Two to four weeks after the last dose of recombinant EphB4-HSA fusion protein, patients undergo robotic-assisted radical cystectomy or robotic-assisted radical or partial nephrectomy.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Cytology Specimen Collection Procedure, Laboratory Biomarker Analysis, Radical Cystectomy, Recombinant EphB4-HSA Fusion Protein, Therapeutic Conventional Surgery
Medical subject headings
Urinary Bladder Neoplasms, Prostatic Neoplasms, Carcinoma, Renal Cell

What participants receive

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

  • Cytology Specimen Collection ProcedureOther

    Also called Cytologic Sampling

    Correlative studies

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Radical CystectomyProcedure or surgery

    Also called Complete Cystectomy

    Undergo robotic-assisted radical cystectomy

  • Recombinant EphB4-HSA Fusion ProteinBiological

    Also called sEphB4-HSA

    Given IV

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo robotic-assisted radical or partial nephrectomy

Study groups in NCT02767921
Study groupRoleWhat they receive
Treatment (recombinant EphB4-HSA fusion protein, surgery)ExperimentalPatients receive recombinant EphB4-HSA fusion protein IV over 60 minutes once weekly for 3 weeks (3 doses) in the absence of disease progression or unacceptable toxicity. Patients who agree may receive the fourth dose after an additional week as determined by the study medical oncologist. Two to four weeks after the last dose of recombinant EphB4-HSA fusion protein, patients undergo robotic-assisted radical cystectomy or robotic-assisted radical or partial nephrectomy.
Receives: Other: Cytology Specimen Collection Procedure; Other: Laboratory Biomarker Analysis; Procedure: Radical Cystectomy; Biological: Recombinant EphB4-HSA Fusion Protein; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Feasibility, defined as the percentage of patients completing at least 3 doses of drug therapy without dose limiting toxicities (DLTs) and who are able to undergo minimally-invasive surgery as planned

    Feasibility is defined for the purpose of this study as >= 90% of patients completing at least 3 doses of drug therapy without DLTs and are able to undergo minimally-invasive surgery as planned.

    Measured: Up to 30 days after the last dose of sEphB4-HSA

  2. Incidence of adverse events graded according to CTCAE version 4 or the Clavien-Dindo classification

    All observed adverse events and complications will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, and time of onset. Tables will be created to summarize these adverse events and complications, overall, by disease cohort, and by phase (neoadjuvant, during surgery, within 30 days post-operative, and days 31-90 post-operative).

    Measured: Up to 90 days post-surgery

Secondary outcomes (2)

  1. Complete pathologic response defined as no residual evidence of invasive disease at the time of cystectomy or nephrectomy

    Pathologic response rates will be calculated and 90% confidence intervals will be constructed.

    Measured: At the time of surgery

  2. Radiologic response as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1

    Radiologic response rates will be calculated and 90% confidence intervals will be constructed.

    Measured: Up to 30 days post-surgery

Timeline

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

  1. First posted11 May 2016 (estimated)
  2. Study start2 Aug 2016
  3. Primary completion28 Jan 2020
  4. Study completion15 Nov 2021

Why it stopped: Insufficient accrual

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02767921
Sponsor's protocol ID
0S-15-6
Other IDs
NCI-2015-02236, 0S-15-6, P30CA014089
Status last verified
Nov 2021
First submitted
6 May 2016
Last updated
24 Nov 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cytology Specimen Collection Procedure, Laboratory Biomarker Analysis and Radical Cystectomy in people with Infiltrating Bladder Urothelial Carcinoma and Recurrent Bladder Carcinoma, run by University of Southern California at 1 site 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 44 inclusion and 0 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: stopped early, as of the sponsor's last update on 24 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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 was stopped early (reason given: Insufficient accrual). Results are not available in the source record.

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?

Feasibility, defined as the percentage of patients completing at least 3 doses of drug therapy without dose limiting toxicities (DLTs) and who are able to undergo minimally-invasive surgery as planned (time frame: Up to 30 days after the last dose of sEphB4-HSA). The study lists 2 primary outcomes in all. 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 NCT02767921.

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 24 Nov 2021.

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