ARRx in Combination With Enzalutamide in Metastatic Castration Resistant Prostate Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: ARRx; Drug: Enzalutamide

Detailed Description

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.

The study was originally registered as a phase 1/ phase 2 study; however, the study was cancelled by the sponsor before opening the phase 2 portion. Outcome measures were updated to include those relevant to the Phase 1 portion as the study was terminated before enrolling into phase 2

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan Rogel Cancer Center
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to understand and voluntarily agree to participate by providing written informed consent for the trial.
• Histologically confirmed prostate adenocarcinoma cancer, either pure or mixed. Small cell/neuroendocrine differentiation is not allowed.
• Castrate levels of serum testosterone (≤ 50 ng/dL). Patients must continue androgen deprivation therapy with an LHRH analogue or antagonist if they have not undergone bilateral orchiectomy.
• Patients must have metastatic disease; either non-measurable disease OR measurable disease per RECIST 1.1.
• Progressive disease despite ongoing treatment with Androgen Deprivation Therapy (ADT).
• Patients treated with first generation anti-androgen as most recent systemic therapy (e.g. bicalutamide, nilutamide) must have at least 4 weeks elapsed from treatment discontinuation to start of protocol therapy with evidence of disease progression (per protocol) following discontinuation of prior anti-androgen.
• Minimum PSA at entry of 1 ng/mL is required.
• ECOG Performance Status 0, 1 or 2.
• Be ≥18 years of age on the day of signing informed consent.
• Demonstrate adequate organ function.
• Subjects must agree to use an adequate method of contraception as outlined in the protocol starting with the time of informed consent through 120 days after the last dose trial therapy.

Exclusion Criteria:

• Prior chemotherapy and/or enzalutamide for metastatic castration-resistant prostate cancer. Chemotherapy administered in the castration-sensitive setting is allowed provided last dose of chemotherapy was greater than 6 months prior to study entry.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to enrollment.
• Has not recovered (i.e., AE ≤Grade 1 or at baseline) from AEs due to a previously administered agent. Subjects with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are an exception to this criterion and are allowed if relevant toxicity is stabilized.
• If subjects received major surgery they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting trial therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. At the time of signing informed consent is a known regular user (including "recreational use") of any illicit drug(s) or had a recent history (within the last year) of drug or alcohol abuse.
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Has received a live virus vaccine within 30 days of planned start of trial therapy.
• Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable brain metastases (stability is normally defined as a period of 1 to 3 months in which there is no evidence of new or enlarging CNS metastases).
• Has symptomatic ascites or pleural effusion; a subject who is clinically stable following treatment for these conditions is eligible.
• Has had a prior allogeneic stem cell or bone marrow transplant.
• Has known contraindication to aspirin (81 mg).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ARRx + Enzalutamide; 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.)

Drug: ARRx; Given intravenously (IV); Other Names: AZD5312; Drug: Enzalutamide; Given by mouth (PO); Other Names: Xtandi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Dose-limiting Toxicity (DLT) During the First Cycle of ARRx (in Combination With Enzalutamide)	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.	Up to day 21 of treatment
Best PSA Response	Number of subjects with at least 50% decline in PSA from Baseline	3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With a Reduction in PSA of at Least 30% From Baseline	Using PCWG3 criteria. Number of patient with a reduction in PSA of at least 30% from baseline	3.5 years
Overall Survival at One Year	One year KM estimate. Patients alive or lost to follow-up at the time of analysis will be censored at their last date of follow-up.	1 year
Intrapatient Dose Delays	Number of participants that experienced dose delays while on study treatment	3.5 years
Intrapatient Dose Reductions	Number of participants that experienced dose reductions while on study treatment	3.5 years

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ajjai Alva, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Actual): January 24, 2023
• Study Completion (Actual): January 24, 2023

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: September 28, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: UMCC 2017.055; HUM00130051 (Other Identifier: University of Michigan); 5P50CA186786-10 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No