OGX-427 in Metastatic Castrate-Resistant Prostate Cancer With Prostate-Specific Antigen Progression While Receiving Abiraterone

The Pacific Clinical Trial: A Randomized Phase II Study Evaluating OGX-427 in Patients With Metastatic Castrate-Resistant Prostate Cancer (MCRPC)Who Have Prostate-Specific Antigen (PSA) Progression While Receiving Abiraterone: Hoosier Oncology Group GU12-159

This Phase II study has been designed to evaluate the anti-tumor effects of adding OGX-427 to continuing abiraterone acetate and prednisone treatment in men with metastatic castrate-resistant prostate cancer (MCRPC) who have prostate-specific antigen (PSA) progression

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer; PSA; Metastatic Castrate-Resistant Prostate Cancer
• Intervention / Treatment: Drug: OGX-427; Drug: Abiraterone Acetate; Drug: Prednisone

Detailed Description

OUTLINE: This is a multi-center study.

This is an open-label, randomized, Phase II clinical trial designed to evaluate the anti-tumor effects of OGX-427 and continuing abiraterone acetate and prednisone versus continuing abiraterone acetate and prednisone alone in men with MCRPC who have evidence of PSA progression but no evidence of symptomatic or radiographic progression that would require alternative therapy (e.g., needing radiation therapy for pain or significant progression of visceral metastases).

Patients on the control arm will be allowed to cross-over to receive OGX-427 following documented disease progression. Patients will be randomized with equal probability to one of the following arms:

EXPERIMENTAL ARM (Arm A):

OGX-427 Starting within 7 days of randomization, three loading doses of 600 mg intravenously (IV) within Week 1 if possible (up to 10 days of initiating treatment), followed by weekly doses of 800 mg IV

Continuation of standard therapy with abiraterone acetate 1000 mg by mouth (PO) daily and prednisone 10-20 mg PO daily

CONTROL ARM (Arm B):

Continuation of standard therapy with abiraterone acetate 1000 mg PO daily and prednisone 10-20 mg PO daily

After documented disease progression, patients on Arm B may opt to receive OGX-427 treatment (according to the Arm A schedule) following a screening evaluation (i.e., all inclusion and exclusion criteria have been met)

Both Arms:

Evaluations at 4 week-intervals. Disease assessments required at the milestone Day 60 assessment (expected to occur after 8 weeks of treatment and prior to Day 1, Week 9) and at 16, 24, 32, 40, and 48 weeks (if applicable) or until documented disease progression. Patients who are withdrawn from the study for a reason other than documented disease progression or patient withdrawal of consent will be followed every 4 weeks in the Off-Treatment Follow-up Period until documented disease progression.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Life Expectancy: Not Specified

Hematopoietic:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109 cells /L, platelet count ≥ 100 x 109 /L, and hemoglobin ≥ 9 g/dL without transfusion

Hepatic:

• Total bilirubin ≤ 1.1 x upper limit of normal (ULN) unless elevated secondary to conditions such as Gilbert's disease, in which case a direct bilirubin ≤ ULN is required
• Serum glutamic pyruvic transaminase (SGPT), alanine transaminase (ALT) and alanine transaminase (SGOT) aspartate transaminase (AST) ≤ 3.0 x ULN

Renal:

• Creatinine ≤ 1.3 x ULN

Cardiac:

• Known left ventricular ejection fraction (LVEF) <50% or New York Heart Association (NYHA) Functional Classification Class III or IV heart failure

Other:

• Castrate serum testosterone level (< 50 ng/dL or < 1.7 nmol/L)
• Potassium within normal limits

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Alberta Health Services: Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Centre Hospitalier de l'Universite de Montreal
• United States
  • California
    • Marina Del Rey, California, United States, 90292
      • Prostate Oncology Specialists, Inc.
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • IU health Bloomington Hospital
    • Goshen, Indiana, United States, 46527
      • IU Health Goshen Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46219
      • IU Health Central Indiana Cancer Centers
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Center: Albuquerque
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Subjects must meet ALL of the following criteria to be eligible for inclusion into the study.

• Histological or cytological diagnosis of adenocarcinoma of the prostate
• Metastatic disease on chest, abdominal, or pelvic computed tomography (CT) scan and/or bone scan

• Currently receiving abiraterone acetate and prednisone and meeting the following criteria:

  • Any PSA decline within 12 weeks from initiation of abiraterone acetate
  • Currently tolerating abiraterone acetate (1000 mg oral daily) and prednisone (10-20 mg oral daily)
  • PSA progression, defined as an increase in PSA which is ≥25% above the nadir and an absolute value of ≥2 ng/mL, which is confirmed by a second value ≥2 weeks later.
  • No evidence of symptomatic or radiographic progression that would require alternative therapy (e.g., needing radiation therapy for pain or significant progression of visceral metastases or >33% increase in daily opioid use within 2 weeks prior to randomization).
• All patients who have not had a surgical orchiectomy must continue treatment with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist to maintain a castrate level of testosterone.

• Patient must fulfill "Prior Therapy" criteria as follows:

  • Chemotherapy: no more than 1 prior chemotherapy regimen for castrate-resistant prostate cancer (CRPC) is permitted; a minimum of at least 28 days must have passed since the last dose of chemotherapy.
  • Hormone therapy: hormonal androgen ablation therapy prior to abiraterone is required.
  • Experimental therapy: prior non-cytotoxic experimental therapy is permitted provided a minimum of at least 14 days has passed since completing therapy. Prior treatment with enzalutamide (MDV3100) is allowed.
  • Radiation: prior external beam radiation is permitted provided a minimum of at least 14 days have passed since completing radiotherapy (exception for radiotherapy: at least 7 days since completing a single fraction of ≤800 cGy to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of randomization
• Must be willing to use effective contraception throughout study treatment and for 3 months after completion of study treatment if able to father a child.
• Must be willing not to change (add or subtract) bone protecting therapy (bisphosphonates and/or denosumab) during the study unless changed for toxicity.
• Written informed consent must be obtained prior to any protocol-specific procedures being performed.

Exclusion Criteria:

Subjects meeting ANY of the following exclusion criteria will NOT be eligible for inclusion into the study:

• Currently receiving abiraterone acetate in combination with any other anti-cancer agent (except prednisone)
• Documented brain metastases, or carcinomatous meningitis, treated or untreated (Brain imaging for asymptomatic patients is not required.)
• Cord compression requiring surgery or radiation therapy while on abiraterone treatment
• Active second malignancy (including lymphoid malignancies such as chronic lymphocytic leukemia or low grade lymphoma) defined, in general, as requiring anticancer therapy or at high risk of recurrence during the study; not including adequately treated non melanomatous skin cancer or other solid tumors curatively treated with no evidence of disease in > 3 years
• History of allergic reactions to therapeutic antisense oligonucleotides
• Active autoimmune disease requiring treatment
• Participated in a prior Phase 3 clinical study evaluating custirsen regardless of study arm assignment (i.e., either control or investigational arm), or prior exposure to OGX-427
• Uncontrolled medical conditions such as myocardial infarction, uncontrolled hypertension, stroke or treatment of a major active infection within 3 months of randomization, as well as any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy
• Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Arm A; OGX-427 + continuation of standard therapy with abiraterone acetate and prednisone	Drug: OGX-427; OGX-427 started within 7 days of randomization, three loading doses of 600 mg IV within Week 1 if possible (up to 10 days of initiating treatment), followed by weekly doses of 800 mg IV; Drug: Abiraterone Acetate; Standard therapy: Abiraterone Acetate 1000 mg PO daily; Drug: Prednisone; Standard therapy: Prednisone 10-20 mg PO daily
Active Comparator: Control Arm: Arm B; Continuation of standard therapy with abiraterone acetate and prednisone	Drug: Abiraterone Acetate; Standard therapy: Abiraterone Acetate 1000 mg PO daily; Drug: Prednisone; Standard therapy: Prednisone 10-20 mg PO daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	To ascertain whether Arm A has a greater proportion of patients observed to be alive without progression at Day 60 (±7 days) as compared to Arm B.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Response	Compare arms to determine the proportion of patients who have a PSA response (≥ 30% decline) and any PSA decline post-randomization.	60 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response	Compare arms to determine the objective response of study patients, per RECIST 1.1	60 days
Time to Disease Progression	Compare arms to determine the time to disease progression of study patients	60 days
Circulating Tumor Cell (CTC) Counts	Compare arms to determine circulating tumor cell (CTC) counts for patients at baseline and while on study	Every 4 weeks
Protein Levels	Compare arms to determine levels of heat shock protein 27 (Hsp27), clusterin, and other relevant proteins of patients at baseline and during study	Every 4 weeks
Phosphatase and Tensin Homolog (PTEN) Deletion Status	Compare arms to determine PTEN deletion status in original pathology specimens correlated with clinical outcomes	Every 4 weeks

Collaborators and Investigators

• Sponsor: Costantine Albany
• Collaborators: Hoosier Cancer Research Network; Achieve Life Sciences
• Investigators: Principal Investigator: Constantine Albany, M.D., Hoosier Cancer Research Network

Publications and helpful links

General Publications

• Kim N. Chi, Christopher Sweeney, Cindy Jacobs, Patricia S. Stewart, Noah M. Hahn. The Pacific trial: A randomized phase II study of OGX-427 in men with metastatic castration-resistant prostate cancer (mCRPC) and PSA progression while receiving abiraterone acetate (AA). J Clin Oncol 31, 2013 (suppl; abstr TPS5101) http://abstracts2.asco.org/AbstView_132_115104.html

Helpful Links

• Hoosier Cancer Research Network Website

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): June 21, 2017
• Study Completion (Actual): June 21, 2017

Study Registration Dates

• First Submitted: September 5, 2012
• First Submitted That Met QC Criteria: September 7, 2012
• First Posted (Estimate): September 10, 2012

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Abiraterone Acetate; OGX-427
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: GU12-159

Plan for Individual participant data (IPD)

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