E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic castrate resistant prostate cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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). An event is having disease progression or death on or before Day 140. NOTE: Day 140, as measured from the date of randomization, will occur normally after Cycle 6 (prior to Cycle 7) study treatment. However, the milestone Day 140 disease assessment must be completed within the inclusive window of Day 125 to Day 155 post-randomization, regardless of the timing of Cycle 6 treatment (e.g., if treatment scheduling at any time has been delayed). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Supplemental Protocol OGX-011-11SP, version1.1, 10 May 2010
Pharmacokinetic and Cardiac Monitoring Study Supplement to Protocol OGX-011-11: A Randomized Phase 3 Study Comparing Standard First-Line Docetaxel/Prednisone to Docetaxel/Prednisone in Combination with Custirsen (OGX-011) in Men with Metastatic Castrate Resistant Prostate Cancer
Objectives: - to determine if custirsen alone or if co-administered with docetaxel alters ECG intervals and morphology with special emphasis on changes in the QTcF interval duration. - to explore if co-administration of docetaxel and custirsen alters the pharmacokinetics of custirsen. - to explore if co-administration of docetaxel and custirsen alters the pharmacokinetics of docetaxel. - to explore the urinary metabolites of custirsen.
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E.3 | Principal inclusion criteria |
Subjects must meet ALL of the following criteria to be eligible for inclusion into the study: 1.Age ≥ 18 years on the date of consent. 2.Histological or cytological diagnosis of adenocarcinoma of the prostate. 3.Metastatic disease on chest, abdominal, or pelvic CT and/or bone scan. 4.Systemic chemotherapy indicated due to progression while on or after androgen ablative therapy defined as: a.Progressive measurable disease: at least a 20% increase in the sum of the longest diameters of measurable lesions over the smallest sum observed –or the appearance of one or more new lesions as assessed by CT scan during hormone ablation treatment. Measurable lesions are nodal or visceral soft-tissue lesions with nodal lesions ≥ 20 mm in diameter or visceral/soft-tissue lesions ≥ 10 mm in diameter (see Section 6.3.1.1). OR b.Bone Scan Progression: appearance of 2 or more new lesions on bone scan during hormone ablation treatment. 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. A minimum starting value of 5.0 ng/mL is required for study randomization. NOTE: Androgen ablative therapy may have included either medical or surgical castration. 5.Baseline laboratory values as stated below: a.Creatinine ≤ 1.5 x upper limit of normal (ULN). b.Bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert’s disease). c.SGOT (AST)≤ 1.5 x ULN. d.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 throughout the study, unless treated with bilateral orchiectomy. 7.Adequate bone marrow function defined at screening as ANC ≥ 1.5 x 109 cells /L and platelet count ≥ 100 x 109 /L. 8.Karnofsky score ≥ 70% (see Appendix 17.2). 9.At least 28 days has 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. 10.At least 4 weeks have passed since receiving any investigational agent at the time of randomization. 11.Has recovered from any other therapy related toxicity to ≤ grade 2, (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy). 12.Patient must be willing to not add, delete or change their current bisphosphonate usage throughout study treatment to assure that adverse event reporting is not confounded by changing their bisphosphonate usage (unless the deletion or change is for toxicity associated with bisphosphonate usage). 13.Patients receiving more than 10 mg of prednisone per day (or steroid equivalent) at screening must be willing to have the dose reduced to 10 mg of prednisone per day for at least 7 days prior to randomization and maintained throughout study treatment. 14.Written informed consent must be obtained prior to any protocol-specific procedures being performed.
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E.4 | Principal exclusion criteria |
Subjects meeting ANY of the following exclusion criteria will NOT be eligible for inclusion into the study: 1.Received any other cytotoxic chemotherapy as treatment. 2.Received any cycling or intermittent hormonal treatment 28 days prior to randomization. 3.Participated in a prior clinical study evaluating custirsen. 4.History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated. (Brain imaging for asymptomatic patients is not required.) 5.Current symptomatic cord compression requiring surgery or radiation therapy. (Once successfully treated and there has been no progression, patients are eligible for the study.) 6.Active second malignancy (except non melanomatous skin or superficial bladder cancer). 7.Uncontrolled medical conditions such as heart failure, 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. 8.Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Survival time distribution: Survival will be assessed for each patient from the date of randomization to the date of death from any cause. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
standard of care treatment: docetaxel (75 mg/M2) + prednisone(5mg BD) |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 79 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Patients should receive study treatment until disease progression, unacceptable toxicity, or completion of 10 cycles is documented. All randomized patients will be followed for survival status and date of death.
All patients who are randomized in the study and receive at least one dose of study treatment (custirsen or docetaxel) must complete an End of Treatment visit. This visit/assessment should be within 21 (± 7) days from withdrawal of study treatment.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |