A study to assess prostate cancer pain with the addition of custirsen

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2010-020802-13-GB
• Date of registration: 08/10/2010
• Prospective Registration: Yes
• Primary sponsor: OncoGenex Technologies, Inc.
• Public title: A study to assess prostate cancer pain with the addition of custirsen
• Scientific title: A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study Evaluating the Pain Palliation Benefit of Adding Custirsen to a Taxane for Second-line Chemotherapy in Men with Castrate Resistant Prostate Cancer - The prostate cancer Saturn study
• Date of first enrolment: 26/04/2011
• Target sample size: 292
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020802-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Teva Pharma GmbH

• Name: Clinical Trial Information Desk
• Affiliation: Teva Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1.Age=18years on the date of consent
2.Histological or cytological diagnosis of adenocarcinoma of the prostate
3.Metastatic disease at screening on a chest, abdomen or pelvic CT or bone scan
4.Concurrent pain and analgesic use that is viewed by the Investigator to be related to prostate cancer
5.Received at least 4cycles of prior docetaxel-based first-line chemotherapy for metastatic disease based on a q3 week schedule of docetaxel(NOTE:patients treated on a weekly or alternate schedule for first-line docetaxel must have received an accumulated dose of docetaxel of at least 300mg/M2)
6.For patients to receive docetaxel retreatment,a response during first-line docetaxel therapy as defined by one or more of the following must have occurred:
a.At least a 30%decrease in the sum of the longest diameter of measurable lesions with no unequivocal progression of existing lesions and no appearance of any new lesions.Measurable disease is defined as either nodes=20 mm or visceral/soft tissue lesions=10 mm
b.PSA response(30% reduction compared to the baseline level prior to initiating first-line docetaxel therapy)
c.Clinical response(classified by the treating Physician or Investigator as a reduction in pain or analgesic use or improvement in performance status).The type and basis of the clinical response(s) must be determined by the Investigator when obtaining the disease history
7.Current progressive disease during or after completing first-line docetaxel treatment as defined by one or more of the criteria below:
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 or after completing first-line docetaxel treatment. Measurable lesions include nodal lesions=20 mm in diameter or visceral/soft-tissue lesions=10 mm in diameter.OR
b.Bone Scan Progression:appearance of 2 or more new lesions on bone scan during or after completing first-line docetaxel treatment.OR
c.Increasing serum PSA level:Three increasing PSA measurements obtained during or after completing first-line docetaxel treatment and 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
8.Baseline laboratory values at screening visit:
a.Creatinine=1.5xupper 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).
9.Must be willing to continue primary androgen suppression with luteinizing hormone releasing hormone (LHRH) analogues throughout the study, if not treated with bilateral orchiectomy
10.Adequate bone marrow function defined as ANC=1.5 x 109 cells /L and platelet count=100 x 109 /L at screening visit
11.Karnofsky score=70%(See Appendix 16.2) at screening visit
12.For patients to receive docetaxel retreatment, at least 6 weeks has passed since receiving the last dose of docetaxel at the time of randomization
13.At least 21days have passed since completing radiotherapy at the time of randomization
14.At least 21days have passed since completing any cytotoxic agent or investigational agent, including ASOs(except custirsen which is an exclusion criterion), at the time of randomization
15.Has recovered from any do
Exclusion criteria:
1.More than two interruptions in first-line docetaxel therapy. An
interruption will be defined as more than 6 weeks between doses.
2.For patients receiving docetaxel retreatment, evidence of disease
progression while on or within 6 weeks of receiving the last dose of firstline
docetaxel therapy based on one of the following:
a.Radiographic imaging (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
or = 2 new lesions on bone scan. Measurable disease is defined as either
nodes = 20 mm or visceral/soft tissue lesions =10 mm.)
b.Clinical deterioration (determined by the treating Physician or
Investigator, when obtaining the disease history, such as clinically
significant pain progression or decreased performance status).
NOTE:Patients with increasing PSA levels while receiving first-line docetaxel are not excluded.
3.Life expectancy less than 12 weeks.
4.Previously participated in any clinical trial evaluating custirsen.
5.Received any other cytotoxic chemotherapy as a second-line treatment after first-line docetaxel-based therapy.
6.Not on any opioid analgesic regimen for their prostate cancer-related
pain
7.Receiving more than one drug within each of the separate categories
of long-acting opioid, short-acting opioid, and non-opioid (See Section
6.6.1)
8.Receiving any analgesic specified in Appendix 16.7.1 as unacceptable
for this study.
9.Received any cycling or intermittent or continuous hormonal treatment 28 days prior to randomization with the exception of the continuous
LHRH analogues required in Inclusion Criteria #9.
10.History of, or current documented brain metastasis or carcinomatous meningitis, treated or untreated. (Brain imaging in asymptomatic patients is not required.)
11.Known epidural disease unless it has been treated and there is no
progression in the treated area.
12.Requiring ongoing treatment during the study with St John's Wort, or with medications known to be either strong CYP3A inhibitors or strong CYP3A inducers (Refer to Section 6.6.11).
13.Active second malignancy (except non melanomatous skin or
superficial bladder cancer) defined as requiring cancer therapy or at high
risk of reoccurrence during the study.
14.Uncontrolled or acute medical conditions such as myocardial
infarction, congestive heart failure, stroke or treatment of a major active infection within 3 months prior to randomization, as well as current uncontrolled hypertension, angina or a serious arrhythmia; and/or significant concurrent medical illness that in the opinion of the
Investigator would preclude protocol therapy.
15.Planned concomitant participation in another clinical trial of an
experimental agent, vaccine or device. Concomitant participation in
observational studies is acceptable.
16.Inability to communicate and read in English, Spanish or French.
Note:Upon review of source documentation, enrollment of a patient who
did not meet the inclusion or exclusion criteria will be classified as a
protocol violation.



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

metastatic castrate resistant prostate cancer
MedDRA version: 14.0 Level: LLT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Custirsen sodium
Product Code: OGX-011
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Custirsen
CAS Number: 685922-56-9
Current Sponsor code: OGX-011
Other descriptive name: Custirsen sodium
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: Docetaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DOCETAXEL
CAS Number: 114977-28-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: JEVTANA
Pharmaceutical Form: Concentrate and solvent for solution for infusion
CAS Number: 183133-96-2
Other descriptive name: CABAZITAXEL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: Ascertain whether patients randomized to the investigational arm have a
longer time to pain progression as compared to patients randomized to
the control arm.

Main Objective: Ascertain whether the investigational arm has a greater proportion of
patients with durable pain palliation as compared to the control arm.

Primary end point(s): The primary endpoint to be ascertained for each patient is whether
durable pain palliation has been observed (yes or no). Durable pain
palliation is defined as having a reduction in pain for a minimum of 12
weeks duration.

Timepoint(s) of evaluation of this end point: The primary endpoint analysis will be based on baseline and study
treatment pain status and analgesic use status until the end of durable
pain palliation status period or pain progression (whichever is first) is
documented. Seven daily assessments are planned at baseline.
Assessments while on study will occur daily for 6 days just prior to Day 1
of each 21-day treatment cycle, starting with the 6-day assessment
interval prior to Day 1, Cycle 2 (see Section 4.2).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Due to the potential for an initial "flare" that can occur within the first
six weeks of treatment, pain progression will be evaluated only after the
completion of Cycle 2 (i.e. after Cycle 3, Day 1), except in cases requiring
radiation for pain palliation prior to completion of Cycle 2.
The secondary objective will be formally analyzed only if the primary
endpoint meets statistical criterion.

Secondary end point(s): Pain progression is defined as having one of the criteria below for two
consecutive assessment intervals :
1.After Cycle 3, Day 1: An increase in the mean worst pain score of
greater than 2 points above the baseline mean worst pain score.
2.After Cycle 3, Day 1: An increase in analgesic usage compared to
baseline levels determined at randomization (regardless of whether the
patient has achieved pain palliation or not) as defined by:
a.an increase in the mean total daily opioid dosage of either the longacting opioid or the short-acting opioid by more than 33%, that is also an increase of more than a 15 mg morphine-equivalent dose above the mean baseline daily dose
OR
b.the addition of any new opioid not previously defined in the baseline
analgesic regimen. (NOTE: This does not include a replacement opioid
for an intolerance or severe adverse event unless the replacement opioid dose is more than 33% above the baseline opioid level using morphineequivalent doses in Table 15)
OR
c.the addition of any new non-opioid not previously defined in the
baseline analgesic regimen with a mean total daily dose > 80% of the
maximum recommended total daily dose (Note: This does not include a
replacement non-opioid for an intolerance or severe adverse event or
changes in dosage for the non-opioid defined in the baseline analgesic
regimen as it will not be considered significant enough to indicate pain
progression)
3.At any time after randomization: Receipt of any radiation therapy for
pain palliation.

Secondary ID(s)

OGX-011-10

2010-020802-13-ES

Source(s) of Monetary Support

Teva Pharmaceuticals Ltd.

OncoGenex Technologies, Inc.

Ethics review

Status: Approved
Approval date:
Contact: