Clinical trial NCT03300505: ARRx in Combination With Enzalutamide in Metastatic Castration Resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostate Cancer
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-10-03
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Subjects With Dose-limiting Toxicity (DLT) During the First Cycle of ARRx (in Combination With Enzalutamide)
timeFrame: Up to day 21 of treatment
measure: Best PSA Response
timeFrame: 3.5 years
Secondary outcomes:
measure: Percentage of Patients With a Reduction in PSA of at Least 30% From Baseline
timeFrame: 3.5 years
measure: Overall Survival at One Year
timeFrame: 1 year
measure: Intrapatient Dose Delays
timeFrame: 3.5 years
measure: Intrapatient Dose Reductions
timeFrame: 3.5 years
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: University of Michigan
name: Ajjai Alva, MD
role: PRINCIPAL_INVESTIGATOR
References: