OGX-427 in Metastatic Castrate-Resistant Prostate Cancer With Prostate-Specific Antigen Progression While Receiving Abiraterone
Condition: Prostate Cancer; Metastatic Castrate-Resistant Prostate Cancer; PSA
MeSH terms: Prostatic Neoplasms
Intervention: OGX-427; Abiraterone Acetate; Prednisone
Intervention description: 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; Standard therapy: Abiraterone Acetate 1000 mg PO daily; Standard therapy: Prednisone 10-20 mg PO daily
Intervention MeSH terms: Prednisone; Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: OGX-427; Abiraterone Acetate

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
    

Eligibility 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.