<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03300505</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2017.055</org_study_id>
    <secondary_id>HUM00130051</secondary_id>
    <nct_id>NCT03300505</nct_id>
  </id_info>
  <brief_title>ARRx in Combination With Enzalutamide in Metastatic Castration Resistant Prostate Cancer</brief_title>
  <official_title>ARRO-CITO: (UMCC 2017.055) Phase Ib/II Single-Arm Multi-Center Study of IONIS-AR-2.5Rx, a Next Generation Androgen Receptor Antisense Oligonucleotide, in Combination With Enzalutamide in Metastatic Castration Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test the effectiveness (how well the drug works), safety, and&#xD;
      tolerability of the investigational drug combination of ARRx (also known as AZD5312) plus&#xD;
      enzalutamide in patients with metastatic castration resistant prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single dose-finding one-arm phase Ib/II trial to determine the maximum tolerated&#xD;
      dose (MTD) from among three dose levels of ARRx in combination with a fixed dose of&#xD;
      enzalutamide and to obtain a preliminary estimate of efficacy at this MTD, as measured by PSA&#xD;
      response rate. Success for the trial is defined as finding a dose level that is likely to be&#xD;
      both tolerable and effective.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Cancelled by the sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">May 31, 2019</start_date>
  <completion_date type="Actual">January 24, 2023</completion_date>
  <primary_completion_date type="Actual">January 24, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with dose-limiting toxicity (DLT) during the first cycle of ARRx (in combination with enzalutamide)</measure>
    <time_frame>Up to day 21 of treatment</time_frame>
    <description>DLTs will be counted based on the number of subjects with DLT at a given dose level. No single subject can trigger more than one DLT event. DLT is defined as any Grade 3 or higher toxicity as defined by CTCAE v5.0. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best PSA response</measure>
    <time_frame>Up to ~3 years</time_frame>
    <description>Using the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. From the start of the treatment until disease progression/recurrence.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to radiographic progression-free survival (rPFS)</measure>
    <time_frame>Up to ~5 years</time_frame>
    <description>Using PCWG3-modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with a reduction in PSA of at least 30% from baseline</measure>
    <time_frame>Up to ~3 years</time_frame>
    <description>Using PCWG3 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to PSA progression</measure>
    <time_frame>Up to ~5 years</time_frame>
    <description>Using PCWG3 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSA progression-free survival (PFS)</measure>
    <time_frame>Up to ~5 years</time_frame>
    <description>PSA PFS is defined as the duration of time from start of treatment to time of PSA progression. PSA progression is defined by PCWG3 criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of therapy (DOT)</measure>
    <time_frame>Up to ~3 years</time_frame>
    <description>Defined by the time interval from the start of treatment to the day of permanent discontinuation of treatment (including death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of PSA Response (DOR)</measure>
    <time_frame>Up to ~5 years</time_frame>
    <description>From the time measurement criteria are met for PSA response until the first date that recurrent or progressive disease is objectively documented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Up to ~5 years</time_frame>
    <description>From start of treatment to time of progression, whether PSA progression by PCWG3 criteria and/or RECIST 1.1 criteria as applicable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to ~5 years</time_frame>
    <description>Defined as the time from the start of treatment until death from any cause. Patients alive or lost to follow-up at the time of analysis will be censored at their last date of follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intrapatient dose delays</measure>
    <time_frame>Up to ~3 years</time_frame>
    <description>Median number of dose delays per patient while on treatment (with minimum and maximum as measures of variability of the statistic)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intrapatient dose reductions</measure>
    <time_frame>Up to ~3 years</time_frame>
    <description>Median number of dose reductions per patient while on treatment (with minimum and maximum as measures of variability of the statistic)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>ARRx + Enzalutamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1b: All registered subjects will be treated with ARRx (ASO) in combination with enzalutamide. ARRx will be given intravenously on Days 1, 4, 8, 11, 15 on cycle 1, then on days 1, 8, 15 in subsequent 21-day cycles. Enzalutamide will be taken daily in 21 day cycles starting Day 1 of cycle 1. Treatment will continue until clinical or radiologic progression or unacceptable toxicity.&#xD;
Phase 2: Subjects will be treated with ARRx (ASO) at the maximum tolerated (MTD), in combination with enzalutamide until clinical or radiologic progression or unacceptable toxicity. (Schedule of administration as in phase 1b.)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ARRx</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>ARRx + Enzalutamide</arm_group_label>
    <other_name>AZD5312</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzalutamide</intervention_name>
    <description>Given by mouth (PO)</description>
    <arm_group_label>ARRx + Enzalutamide</arm_group_label>
    <other_name>Xtandi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to understand and voluntarily agree to participate by providing written&#xD;
             informed consent for the trial.&#xD;
&#xD;
          -  Histologically confirmed prostate adenocarcinoma cancer, either pure or mixed. Small&#xD;
             cell/neuroendocrine differentiation is not allowed.&#xD;
&#xD;
          -  Castrate levels of serum testosterone (≤ 50 ng/dL). Patients must continue androgen&#xD;
             deprivation therapy with an LHRH analogue or antagonist if they have not undergone&#xD;
             bilateral orchiectomy.&#xD;
&#xD;
          -  Patients must have metastatic disease; either non-measurable disease OR measurable&#xD;
             disease per RECIST 1.1.&#xD;
&#xD;
          -  Progressive disease despite ongoing treatment with Androgen Deprivation Therapy (ADT).&#xD;
&#xD;
          -  Patients treated with first generation anti-androgen as most recent systemic therapy&#xD;
             (e.g. bicalutamide, nilutamide) must have at least 4 weeks elapsed from treatment&#xD;
             discontinuation to start of protocol therapy with evidence of disease progression (per&#xD;
             protocol) following discontinuation of prior anti-androgen.&#xD;
&#xD;
          -  Minimum PSA at entry of 1 ng/mL is required.&#xD;
&#xD;
          -  ECOG Performance Status 0, 1 or 2.&#xD;
&#xD;
          -  Be ≥18 years of age on the day of signing informed consent.&#xD;
&#xD;
          -  Demonstrate adequate organ function.&#xD;
&#xD;
          -  Subjects must agree to use an adequate method of contraception as outlined in the&#xD;
             protocol starting with the time of informed consent through 120 days after the last&#xD;
             dose trial therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior chemotherapy and/or enzalutamide for metastatic castration-resistant prostate&#xD;
             cancer. Chemotherapy administered in the castration-sensitive setting is allowed&#xD;
             provided last dose of chemotherapy was greater than 6 months prior to study entry.&#xD;
&#xD;
          -  Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigation device&#xD;
             within 4 weeks prior to enrollment.&#xD;
&#xD;
          -  Has not recovered (i.e., AE ≤Grade 1 or at baseline) from AEs due to a previously&#xD;
             administered agent. Subjects with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are an&#xD;
             exception to this criterion and are allowed if relevant toxicity is stabilized.&#xD;
&#xD;
          -  If subjects received major surgery they must have recovered adequately from the&#xD;
             toxicity and/or complications from the intervention prior to starting trial therapy.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial. At the time of signing informed&#xD;
             consent is a known regular user (including &quot;recreational use&quot;) of any illicit drug(s)&#xD;
             or had a recent history (within the last year) of drug or alcohol abuse.&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
          -  Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
          -  Has received a live virus vaccine within 30 days of planned start of trial therapy.&#xD;
&#xD;
          -  Has known active CNS metastases and/or carcinomatous meningitis. Subjects with&#xD;
             previously treated brain metastases may participate provided they have stable brain&#xD;
             metastases (stability is normally defined as a period of 1 to 3 months in which there&#xD;
             is no evidence of new or enlarging CNS metastases).&#xD;
&#xD;
          -  Has symptomatic ascites or pleural effusion; a subject who is clinically stable&#xD;
             following treatment for these conditions is eligible.&#xD;
&#xD;
          -  Has had a prior allogeneic stem cell or bone marrow transplant.&#xD;
&#xD;
          -  Has known contraindication to aspirin (81 mg).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ajjai Alva, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Rogel Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03300505
org study id: UMCC 2017.055
secondary id: HUM00130051
nct id: NCT03300505
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test the effectiveness (how well the drug works), safety, and
      tolerability of the investigational drug combination of ARRx (also known as AZD5312) plus
      enzalutamide in patients with metastatic castration resistant prostate cancer.
This is a single dose-finding one-arm phase Ib/II trial to determine the maximum tolerated
      dose (MTD) from among three dose levels of ARRx in combination with a fixed dose of
      enzalutamide and to obtain a preliminary estimate of efficacy at this MTD, as measured by PSA
      response rate. Success for the trial is defined as finding a dose level that is likely to be
      both tolerable and effective.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects with dose-limiting toxicity (DLT) during the first cycle of ARRx (in combination with enzalutamide)
time frame: Up to day 21 of treatment
description: DLTs will be counted based on the number of subjects with DLT at a given dose level. No single subject can trigger more than one DLT event. DLT is defined as any Grade 3 or higher toxicity as defined by CTCAE v5.0. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition.
measure: Best PSA response
time frame: Up to ~3 years
description: Using the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. From the start of the treatment until disease progression/recurrence.
measure: Time to radiographic progression-free survival (rPFS)
time frame: Up to ~5 years
description: Using PCWG3-modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).
measure: Percentage of patients with a reduction in PSA of at least 30% from baseline
time frame: Up to ~3 years
description: Using PCWG3 criteria
measure: Time to PSA progression
time frame: Up to ~5 years
description: Using PCWG3 criteria
measure: PSA progression-free survival (PFS)
time frame: Up to ~5 years
description: PSA PFS is defined as the duration of time from start of treatment to time of PSA progression. PSA progression is defined by PCWG3 criteria.
measure: Duration of therapy (DOT)
time frame: Up to ~3 years
description: Defined by the time interval from the start of treatment to the day of permanent discontinuation of treatment (including death).
measure: Duration of PSA Response (DOR)
time frame: Up to ~5 years
description: From the time measurement criteria are met for PSA response until the first date that recurrent or progressive disease is objectively documented.
measure: Progression-free survival
time frame: Up to ~5 years
description: From start of treatment to time of progression, whether PSA progression by PCWG3 criteria and/or RECIST 1.1 criteria as applicable.
measure: Overall survival
time frame: Up to ~5 years
description: Defined as the time from the start of treatment until death from any cause. Patients alive or lost to follow-up at the time of analysis will be censored at their last date of follow-up.
measure: Intrapatient dose delays
time frame: Up to ~3 years
description: Median number of dose delays per patient while on treatment (with minimum and maximum as measures of variability of the statistic)
measure: Intrapatient dose reductions
time frame: Up to ~3 years
description: Median number of dose reductions per patient while on treatment (with minimum and maximum as measures of variability of the statistic)
arm group label: ARRx + Enzalutamide
arm group type: Experimental
description: Phase 1b: All registered subjects will be treated with ARRx (ASO) in combination with enzalutamide. ARRx will be given intravenously on Days 1, 4, 8, 11, 15 on cycle 1, then on days 1, 8, 15 in subsequent 21-day cycles. Enzalutamide will be taken daily in 21 day cycles starting Day 1 of cycle 1. Treatment will continue until clinical or radiologic progression or unacceptable toxicity.
Phase 2: Subjects will be treated with ARRx (ASO) at the maximum tolerated (MTD), in combination with enzalutamide until clinical or radiologic progression or unacceptable toxicity. (Schedule of administration as in phase 1b.)
intervention type: Drug
intervention name: ARRx
description: Given intravenously (IV)
arm group label: ARRx + Enzalutamide
other name: AZD5312
intervention type: Drug
intervention name: Enzalutamide
description: Given by mouth (PO)
arm group label: ARRx + Enzalutamide
other name: Xtandi
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ajjai Alva, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
sharing ipd: No