ARRx in Combination With Enzalutamide in Metastatic Castration Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT03300505|
Recruitment Status : Suspended (Enrollment and/or interactions/interventions temporarily paused due to COVID-19 and expected to resume in the future. This is not a suspension of IRB approval.)
First Posted : October 3, 2017
Last Update Posted : May 1, 2020
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: ARRx Drug: Enzalutamide||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||May 31, 2019|
|Estimated Primary Completion Date :||May 2024|
|Estimated Study Completion Date :||May 2024|
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.)
Given intravenously (IV)
Other Name: AZD5312
Given by mouth (PO)
Other Name: Xtandi
- 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 ]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.
- Best PSA response [ Time Frame: Up to ~3 years ]Using the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. From the start of the treatment until disease progression/recurrence.
- Time to radiographic progression-free survival (rPFS) [ Time Frame: Up to ~5 years ]Using PCWG3-modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).
- Percentage of patients with a reduction in PSA of at least 30% from baseline [ Time Frame: Up to ~3 years ]Using PCWG3 criteria
- Time to PSA progression [ Time Frame: Up to ~5 years ]Using PCWG3 criteria
- PSA progression-free survival (PFS) [ Time Frame: Up to ~5 years ]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.
- Duration of therapy (DOT) [ Time Frame: Up to ~3 years ]Defined by the time interval from the start of treatment to the day of permanent discontinuation of treatment (including death).
- Duration of PSA Response (DOR) [ Time Frame: Up to ~5 years ]From the time measurement criteria are met for PSA response until the first date that recurrent or progressive disease is objectively documented.
- Progression-free survival [ Time Frame: Up to ~5 years ]From start of treatment to time of progression, whether PSA progression by PCWG3 criteria and/or RECIST 1.1 criteria as applicable.
- Overall survival [ Time Frame: Up to ~5 years ]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.
- Intrapatient dose delays [ Time Frame: Up to ~3 years ]Median number of dose delays per patient while on treatment (with minimum and maximum as measures of variability of the statistic)
- Intrapatient dose reductions [ Time Frame: Up to ~3 years ]Median number of dose reductions per patient while on treatment (with minimum and maximum as measures of variability of the statistic)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03300505
|United States, Michigan|
|University of Michigan Rogel Cancer Center|
|Ann Arbor, Michigan, United States, 48105|
|Principal Investigator:||Ajjai Alva, MD||University of Michigan|