A Study Evaluating the Pain Palliation Benefit of Adding Custirsen to Docetaxel Retreatment or Cabazitaxel as Second Line Therapy in Men With Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Tracking Information
First Submitted Date ICMJE	February 26, 2010
First Posted Date ICMJE	March 10, 2010
Last Update Posted Date	October 12, 2016
Study Start Date ICMJE	March 2010
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 14, 2011)	To ascertain whether the investigational arm has a greater proportion of patients with durable pain palliation as compared to the control arm. [ Time Frame: 3 to 6 months ]
Original Primary Outcome Measures ICMJE; (submitted: March 8, 2010)	To ascertain whether the investigational arm has a greater proportion of patients with durable pain palliation as compared to the control arm. [ Time Frame: 12 weeks ]
Change History	Complete list of historical versions of study NCT01083615 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 8, 2010)	To ascertain whether patients randomized to the investigational arm have a longer time to pain progression as compared to patients randomized to the control arm. [ Time Frame: 6 months. ]; Safety [ Time Frame: 6 months ]Comparison of treatment arms with respect to the incidence of serious adverse events and the incidence of grade 3 or higher adverse events.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study Evaluating the Pain Palliation Benefit of Adding Custirsen to Docetaxel Retreatment or Cabazitaxel as Second Line Therapy in Men With Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Official Title ICMJE	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 Resistance Prostate Cancer
Brief Summary	The purpose of this study is to determine if the addition of study drug (custirsen) can provide durable pain palliation for castrate resistant prostate cancer patients receiving docetaxel retreatment or cabazitaxel as a second line therapy.
Detailed Description	This is a randomized, double-blind, placebo-controlled, multicenter, international trial enrolling patients with metastatic CRPC who had a response to first-line docetaxel therapy and have prostate cancer-related pain with progression of disease. The intended intervention is second-line treatment with docetaxel retreatment or cabazitaxel plus study agent, where custirsen is to be administered in the investigational arm and placebo is to be administered in the control arm. Selection of the chemotherapy (docetaxel re-treatment or cabazitaxel) is to be determined by the treating physician, based on the patient's first-line response. The study will primarily assess pain and analgesic use for evaluation of durable pain palliation in response to study treatment. Pain and analgesic use will be obtained via a 3rd party contact center (direct contact with patient). Study treatment starts with a Loading Dose Period during which three infusions of study agent (custirsen vs. placebo) will be administered. Following the Loading Dose Period, study treatment will consist of docetaxel or cabazitaxel on a 21-day cycle with weekly study agent (custirsen vs. placebo) infusions on Day 1, 8 and 15 of each 21-day cycle and oral prednisone BID. Patients will continue study treatment until pain progression, unacceptable toxicity, completion of 10 cycles or other specific criteria for withdrawal identified in the protocol. If study treatment is completed or discontinued prior to pain progression, 6-day assessments will continue every 3 weeks until pain progression is documented. Follow-up after study treatment will occur for safety parameters for 3 weeks after the last study agent infusion in all patients. Survival status updates are to be reported every 12 weeks following documentation of pain progression. The amount of time that patients remain on the study will vary; but the average survival of these patients who receive second line taxane treatment is expected to be 14 to 15 months.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Castrate-Resistant Prostate Cancer; Hormone Refractory Prostate Cancer
Intervention ICMJE	Drug: custirsen sodium An antisense oligonucleotide that blocks production of clusterin Other Name: OGX-011; Drug: isotonic, 0.9% sodium chloride Placebo for custirsen sodium; Drug: docetaxel; Drug: cabazitaxel; Drug: prednisone
Study Arms	Experimental: Custirsen Study treatment starts with a Loading Dose Period (1 week) during which 3 infusions of custirsen will be administered. Following the Loading Dose Period, study treatment will consist of docetaxel (75 mg/m2 total dose) or cabazitaxel (25 mg/m2 total dose) on a 21-day cycle with weekly custirsen infusions (640 mg total dose) on Day 1, 8 and 15 of each 21-day cycle and oral prednisone BID. Participants will continue study treatment until pain progression, unacceptable toxicity, completion of 10 cycles or other specific criteria for withdrawal identified in the protocol. Interventions: Drug: custirsen sodium Drug: docetaxel Drug: cabazitaxel Drug: prednisone; Placebo Comparator: Placebo Study treatment starts with a Loading Dose Period (1 week) during which 3 infusions of placebo (isotonic, 0.9% sodium chloride) will be administered. Following the Loading Dose Period, study treatment will consist of docetaxel (75 mg/m2 total dose) or cabazitaxel (25 mg/m2 total dose) on a 21-day cycle with weekly placebo infusions on Day 1, 8 and 15 of each 21-day cycle and oral prednisone BID. Participants will continue study treatment until pain progression, unacceptable toxicity, completion of 10 cycles or other specific criteria for withdrawal identified in the protocol. Interventions: Drug: isotonic, 0.9% sodium chloride Drug: docetaxel Drug: cabazitaxel Drug: prednisone
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: February 11, 2014)	14
Original Estimated Enrollment ICMJE; (submitted: March 8, 2010)	292
Actual Study Completion Date	March 2013
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria; Age ≥ 18 years on the date of consent.; Histological or cytological diagnosis of adenocarcinoma of the prostate.; Metastatic disease at screening on a chest, abdomen or pelvic CT or bone scan.; Concurrent pain and analgesic use that is viewed by the Investigator to be related to prostate cancer.; Received at least 4 cycles of prior docetaxel-based first-line chemotherapy for metastatic disease based on a q3 week schedule of docetaxel. Patients treated on a weekly or alternate schedule for first-line docetaxel must have received an accumulated dose of docetaxel of at least 300 mg/M2.; Current progressive disease during or after completing first-line docetaxel treatment.; Baseline laboratory values at screening visit within protocol defined limits.; Must be willing to continue primary androgen suppression with luteinizing hormone releasing hormone (LHRH) analogues throughout the study, if not treated with bilateral orchiectomy.; Adequate bone marrow function.; Karnofsky score ≥ 70% at screening visit.; At least 21 days have passed since completing radiotherapy at the time of randomization.; At least 21 days have passed since completing any cytotoxic agent or investigational agent given in combination with the docetaxel-based first-line therapy, including ASOs (except custirsen which is an exclusion criterion), at the time of randomization.; Has recovered from all therapy related toxicity to ≤ grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy).; Patient can tolerate a starting dose of docetaxel of 75 mg/M2 or cabazitaxel at 25 mg/M2.; Patient must have remained on the same bisphosphonate or denosumab usage for a minimum of 12 weeks prior to randomization.; Written informed consent must be obtained prior to any protocol-specific procedures being performed. Exclusion Criteria; More than two interruptions in first-line docetaxel therapy. An interruption will be defined as more than 6 weeks between doses.; Life expectancy less than 12 weeks.; Previously participated in any clinical trial evaluating custirsen.; Received any other cytotoxic chemotherapy as a second-line treatment after first-line docetaxel-based therapy.; Not on any opioid analgesic regimen for their prostate cancer-related pain.; Receiving more than one drug within each of the separate categories of long-acting opioid, short-acting opioid, and non-opioid.; Receiving any analgesic specified in the protocol as unacceptable for this study.; Planned concomitant participation in another clinical trial of an experimental agent, vaccine or device. Concomitant participation in observational studies is acceptable.; Inability to communicate and read in English, Spanish or French.
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years to 99 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, France, Spain, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01083615
Other Study ID Numbers ICMJE	OGX-011-10
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Achieve Life Sciences
Study Sponsor ICMJE	Achieve Life Sciences
Collaborators ICMJE	Teva Pharmaceuticals USA
Investigators ICMJE	Principal Investigator: Tomasz M Beer, M.D. Oregon Health and Science University Principal Investigator: Sebastien J Hotte, M.D. Juravinski Cancer Centre, McMaster University Principal Investigator: Karim Fizazi, M.D., Ph.D. Institut Gustave Roussy, University of Paris
PRS Account	Achieve Life Sciences
Verification Date	October 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP