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)

Sponsor

Achieve Life Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT01083615

Collaborator

Teva Pharmaceuticals USA (Industry)

Enrollment

Locations

Arms

Duration (Months)

0.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Castrate-Resistant Prostate Cancer Hormone Refractory Prostate Cancer	Drug: custirsen sodium Drug: isotonic, 0.9% sodium chloride Drug: docetaxel Drug: cabazitaxel Drug: prednisone	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official 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 Resistance Prostate Cancer

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: custirsen sodium An antisense oligonucleotide that blocks production of clusterin Other Names: OGX-011 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.	Drug: isotonic, 0.9% sodium chloride Placebo for custirsen sodium Drug: docetaxel Drug: cabazitaxel Drug: prednisone

Arm

Intervention/Treatment

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.

Drug: custirsen sodium

An antisense oligonucleotide that blocks production of clusterin

Other Names:

OGX-011

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.

Drug: isotonic, 0.9% sodium chloride

Placebo for custirsen sodium

Drug: docetaxel

Drug: cabazitaxel

Drug: prednisone

Outcome Measures

Primary Outcome Measures

To ascertain whether the investigational arm has a greater proportion of patients with durable pain palliation as compared to the control arm. [3 to 6 months]

Secondary Outcome Measures

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. [6 months.]
Safety [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	La Verne	California	United States	91705
2	Ft. Lauderdale	Florida	United States	33308
3	Tampa	Florida	United States	33612
4	Honolulu	Hawaii	United States	96813
5	Urbana	Illinois	United States	61801
6	Metairie	Louisiana	United States	70006
7	Baltimore	Maryland	United States	21201
8	Burlington	Massachusetts	United States	01805
9	Detroit	Michigan	United States	48201
10	Kansas City	Missouri	United States	64132
11	Omaha	Nebraska	United States	68130
12	Las Vegas	Nevada	United States	89169
13	Syracuse	New York	United States	13210
14	Raleigh	North Carolina	United States	27607
15	Canton	Ohio	United States	44718
16	Oklahoma City	Oklahoma	United States	73120
17	Portland	Oregon	United States	97239
18	Columbia	South Carolina	United States	29209
19	Memphis	Tennessee	United States	38120
20	Tyler	Texas	United States	75701
21	Winnipeg	Manitoba	Canada	R3E 0V9
22	Hamilton	Ontario	Canada	L8V 5C2
23	Lyon		France
24	Paris		France
25	Saint Herblain		France
26	Villejuif		France
27	Barcelona		Spain
28	Madrid		Spain
29	Pamplona		Spain
30	Sabadell		Spain
31	Valencia		Spain
32	Cambridge		United Kingdom
33	Sutton		United Kingdom

Sponsors and Collaborators

Achieve Life Sciences
Teva Pharmaceuticals USA

Investigators

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