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

• ClinicalTrials.gov Identifier: NCT01681433
• Recruitment Status: Terminated
• First Posted: September 10, 2012
• Results First Posted: October 18, 2018
• Last Update Posted: October 18, 2018
• Sponsor: Costantine Albany
• Collaborators: Hoosier Cancer Research Network; Achieve Life Sciences
• Information provided by (Responsible Party): Costantine Albany, Hoosier Cancer Research Network

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Prostate Cancer; Metastatic Castrate-Resistant Prostate Cancer; PSA	Drug: OGX-427; Drug: Abiraterone Acetate; Drug: Prednisone	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 2012
• Actual Primary Completion Date: June 21, 2017
• Actual Study Completion Date: June 21, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival [ Time Frame: 60 days ]
   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.

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Prostate Oncology Specialists, Inc.

Marina Del Rey, California, United States, 90292

United States, Indiana

IU Health Bloomington Hospital

Bloomington, Indiana, United States, 47403

IU Health Goshen Hospital

Goshen, Indiana, United States, 46527

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States, 46202

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, United States, 46219

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States, 46601

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, New Mexico

University of New Mexico Cancer Center: Albuquerque

Albuquerque, New Mexico, United States, 87131

United States, Virginia

Virginia Oncology Associates

Norfolk, Virginia, United States, 23502

Canada, Alberta

Alberta Health Services: Tom Baker Cancer Centre

Calgary, Alberta, Canada, T2N 4N2

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

BC Cancer Agency

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Manitoba

Cancer Care Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Ontario

Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

Canada, Quebec

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada, H2L 4M1

Sponsors and Collaborators

Costantine Albany

Hoosier Cancer Research Network

Achieve Life Sciences

Investigators

• Principal Investigator: Constantine Albany, M.D.; Hoosier Cancer Research Network

  Study Documents (Full-Text)

Documents provided by Costantine Albany, Hoosier Cancer Research Network:

Study Protocol and Statistical Analysis Plan  [PDF] July 21, 2014

More Information

Additional Information:

Hoosier Cancer Research Network Website 

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

• Responsible Party: Costantine Albany, Sponsor-Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT01681433
• Other Study ID Numbers: GU12-159
• First Posted: September 10, 2012
• Results First Posted: October 18, 2018
• Last Update Posted: October 18, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Costantine Albany, Hoosier Cancer Research Network:

OGX-427; Abiraterone Acetate

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Prednisone; Abiraterone Acetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors