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| ID | Type | Description | Link |
|---|---|---|---|
| HUM00130051 | Other Identifier | University of Michigan | |
| 5P50CA186786-10 | U.S. NIH Grant/Contract | View source |
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Cancelled by the sponsor
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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.) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARRx | Drug | Given intravenously (IV) |
|
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ajjai Alva, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Rogel Cancer Center | Ann Arbor | Michigan | 48105 | United States | ||
| Barbara Ann Karmanos Cancer Institute |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Level 1: 600 mg IONIS | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| FG001 | Dose Level 2: 750 mg IONIS | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| FG002 | Dose Level 3: 900 mg IONIS | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Level 1 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Posted | Count of Participants | Participants | Up to day 21 of treatment |
|
All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment; additionally, any serious adverse event occurring more than 30 days after the last study treatment if considered to be related to the study treatment. Data was collected during a 3.5 year period.
Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Level 1 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Back Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin | University of Michigan Rogel Cancer Center | 734-936-9499 | ClinicalTrialsgov_CCAdmin@umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 5, 2021 | May 14, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 4, 2019 | May 14, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C540278 | enzalutamide |
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| Enzalutamide | Drug | Given by mouth (PO) |
|
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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 |
| Detroit |
| Michigan |
| 48201 |
| United States |
| Sponsor Termination |
|
| Adverse Event |
|
| BG001 | Dose Level 2 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| BG002 | Dose Level 3 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| BG003 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Sex: Female, Male | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Count of Participants | Participants |
|
| Race (NIH/OMB) | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Count of Participants | Participants |
|
| Region of Enrollment | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Number | participants |
|
| OG001 | Level 2 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
| OG002 | Level 3 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS |
|
|
| Primary | Best PSA Response | Number of subjects with at least 50% decline in PSA from Baseline | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Posted | Count of Participants | Participants | 3.5 years |
|
|
|
| Secondary | 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 | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Posted | Count of Participants | Participants | 3.5 years |
|
|
|
| Secondary | 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. | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year |
|
|
|
| Secondary | Intrapatient Dose Delays | Number of participants that experienced dose delays while on study treatment | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Posted | Count of Participants | Participants | 3.5 years |
|
|
|
| Secondary | Intrapatient Dose Reductions | Number of participants that experienced dose reductions while on study treatment | Only a single participant was included in the Dose Level 1 arm and data are not reported publicly to protect participant confidentiality | Posted | Count of Participants | Participants | 3.5 years |
|
|
|
| 0 |
| 0 |
| 0 |
| 1 |
| 0 |
| 0 |
| EG001 | Level 2 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS | 1 | 5 | 2 | 5 | 5 | 5 |
| EG002 | Level 3 | 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. ARRx: Given intravenously (IV) Enzalutamide: Given by mouth (PO) Dose Level 1: 600 mg IONIS Dose Level 2: 750 mg IONIS Dose Level 3: 900 mg IONIS | 0 | 3 | 1 | 3 | 3 | 3 |
| Acute Kidney Injury | Renal and urinary disorders | Non-systematic Assessment |
|
| Thromboembolic Event | Vascular disorders | Non-systematic Assessment |
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| Sepsis | General disorders | Non-systematic Assessment |
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| Fever | General disorders | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Blood lactate dehydrogenase increased | Investigations | Non-systematic Assessment |
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| Bruising | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Bullous dermatitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Chills | General disorders | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | Non-systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Edema limbs | General disorders | Non-systematic Assessment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Fever | General disorders | Non-systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Flu like symptoms | General disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Hot flashes | Vascular disorders | Non-systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hypoalbuminemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | Non-systematic Assessment |
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| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Pain | General disorders | Non-systematic Assessment |
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| Paresthesia | Nervous system disorders | Non-systematic Assessment |
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| Thromboembolic event | Vascular disorders | Non-systematic Assessment |
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| Urinary retention | Renal and urinary disorders | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Weight loss | Investigations | Non-systematic Assessment |
|
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| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
|
| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
|