ARRx in Combination With Enzalutamide in Metastatic Castration Resistant Prostate Cancer

NCT03300505 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: UMCC 2017.055HUM001300515P50CA186786-10
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Percentage of Patients With a Reduction in PSA of at Least 30% From Baseline

  3.5 years

• Overall Survival at One Year

  1 year

• Intrapatient Dose Delays

  3.5 years

• Intrapatient Dose Reductions

  3.5 years

Study Arms (1)

ARRx + Enzalutamide

EXPERIMENTAL

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; Drug: Enzalutamide

Interventions

ARRx DRUG

Given intravenously (IV)

Also known as: AZD5312

ARRx + Enzalutamide

Enzalutamide DRUG

Given by mouth (PO)

Also known as: Xtandi

ARRx + Enzalutamide

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48105, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

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: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Ajjai Alva, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 3, 2017
• Study Start: May 31, 2019
• Primary Completion: January 24, 2023
• Study Completion: January 24, 2023
• Last Updated: May 13, 2025
• Results First Posted: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)