The trial is designed to determine the efficacy of Custirsen (OGX-011) in combination with Cabazitaxel/Prednisone versus Cabazitaxel/Prednisone alone in Men with Metastatic Castrate Resistant Prostate Cancer

Phase 1

Conditions: Metastatic Castrate Resistant Prostate Cancer
MedDRA version: 18.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.1Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-001461-32-HU

Lead Sponsor: OncoGenex Technologies Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 630

Inclusion Criteria

1.Histological or cytological diagnosis of adenocarcinoma of the prostate

2.Metastatic disease on chest, abdominal, or pelvic CT scan (CT preferred but MRI acceptable) and/or bone scan

3.Previous first-line treatment for CRPC with a docetaxel-containing regimen. Patients must have received at least =225 mg/m2 of docetaxel (i.e., 3 cycles of 75 mg/m2).

4.Current progressive disease defined by one or more of the criteria below:
a.Progressive measurable disease by RECIST 1.1: At least a 20% increase in the sum of the diameters of measurable lesions over the smallest sum observed or the appearance of one or more new lesions as assessed by CT scan.
OR
b.Bone scan progression: Appearance of 2 or more new lesions on bone scan
OR
c.Increasing serum PSA level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable. For patients who progress based only on increasing serum PSA level, a minimum starting value of 5.0 ng/mL is required for study randomization.

5.Baseline laboratory values as stated below:
a.ANC = 1.5 x 10^9 cells /L
b.Platelet count = 125 x 10^9 /L
c.Creatinine = 1.5 x upper limit of normal (ULN)
d.Bilirubin = 1.1 x ULN (unless elevated secondary to conditions such as Gilbert’s disease)
e.SGOT (AST) and SGPT (ALT) = 1.5 x ULN
f.Castrate serum testosterone level (< 50 ng/dL -or- <1.7 nmol/L)

6.Must be willing to continue primary androgen suppression with gonadotropin-releasing hormone (GnRH) analogues (either agonists or antagonists) throughout the study, unless treated with bilateral orchiectomy

7.Karnofsky score = 70%

8.At least 21 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

9.At least 21 days have passed since receiving any investigational agent at the time of randomization

10.At least 21 days have passed since major surgery

11.Has recovered from any docetaxel therapy-related neuropathy to = grade 1 at the time of randomization

12.Has recovered from all therapy related toxicity to =grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy) at the time of randomization

13.Able to tolerate a starting dose of 25 mg/m2 cabazitaxel

14.Willing to not add, delete, or change their current bisphosphonate or denosumab usage throughout study treatment to assure that adverse event reporting is not confounded by changing their bisphosphonate or denosumab usage (unless withdrawn or changed as a result of bisphosphonate or denosumab associated toxicity)

15.Able to tolerate oral prednisone at 10 mg per day. NOTE: If receiving more than 10 mg of prednisone per day (or steroid equivalent) at screening, must be able to have the dose reduced to 10 mg of prednisone per day prior to randomization and throughout study treatment. Patients not receiving prednisone at screening need to begin oral prednisone of 10 mg per day prior to or on the morning of Day 1 of Cycle 1.

16.Competent and willing to provide written informed consent prior to any protocol-specific procedures being performed.

Are the trial subjects under 18? no
Number of subjects f

Exclusion Criteria

1.Received any other cytotoxic chemotherapy beyond the first-line docetaxel-containing regimen as treatment for prostate cancer

2.Received prior radioisotope with strontium 89 or samarium 153

3.Received any cycling, intermittent, or continuous hormonal treatment within 21 days prior to randomization with the exception of the continuous GnRH analogues required in Inclusion Criteria #6. Note: Prior treatment with abiraterone or MDV3100 is allowed as long as 21 days have passed since last dose.

4.Participated in a prior Phase 3 clinical study evaluating custirsen regardless of study arm assignment (i.e. either control or investigational arm)

5.Requiring ongoing treatment during the study with medications known to be either strong cytochrome P3A (CYP3A) inhibitors or strong CYP3A inducers (Refer to Section 6.5.10). NOTE: The washout period for these medications and St John’s Wort must be at least one week from randomization.

6.History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated (Brain imaging for asymptomatic patients is not required).

7.Current symptomatic cord compression requiring surgery or radiation therapy (Once successfully treated and there has been no progression, patients are eligible for the study).

8.Active second malignancy, including lymphoid malignancies such as chronic lymphocytic leukemia or low grade lymphoma (except non melanomatous skin or superficial bladder cancer) defined in general as requiring anticancer therapy or at high risk of recurrence during the study

9.Uncontrolled medical conditions such as diabetes mellitus, congestive heart failure, angina pectoris, serious cardiac arrhythmia, severe hypertension, or active infection requiring systemic antibiotics, or any event such as myocardial infarction, cerebrovascular accident, or pulmonary embolism within 3 months of randomization, as well as any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy

10.Known severe hypersensitivity to taxanes or polysorbate 80-containing drugs

11.Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: There are co-primary objectives for this study: To ascertain whether the survival time distribution for patients randomized to the investigational arm is consistent with longer survival as compared to patients randomized to the control arm for (1) all randomized<br>patients and (2) patients identified as having poor prognosis.<br>;Secondary Objective: To compare the arms with respect to the proportion of patients having a milestone Day 140 status of Alive Without Event (within the window of Day 125-155 post-randomization). <br>An event is defined as disease progression or death on or before Day 140. ;Primary end point(s): Primary Efficacy Endpoint is Survival time ;Timepoint(s) of evaluation of this end point: Survival time will be assessed for each patient from the date of randomization to the date of death from any cause.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Alive Without Event (AWE) is determined if a patient is alive and found to be free of evidence of disease progression;Timepoint(s) of evaluation of this end point: The status of each patient at approximately day 140 (window of Day~125-155) post randomization

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