Clinical trial NCT01083615: 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: 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Castrate-Resistant Prostate Cancer
Hormone Refractory Prostate Cancer
Keywords: CRPC patients with cancer related pain
CRPC
HRPC
Lead sponsor: Achieve Life Sciences
Sponsor class: INDUSTRY
Collaborators: name: Teva Pharmaceuticals USA
First posted: 2010-03-10
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

1. Age ≥ 18 years 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 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.
6. Current progressive disease during or after completing first-line docetaxel treatment.
7. Baseline laboratory values at screening visit within protocol defined limits.
8. Must be willing to continue primary androgen suppression with luteinizing hormone releasing hormone (LHRH) analogues throughout the study, if not treated with bilateral orchiectomy.
9. Adequate bone marrow function.
10. Karnofsky score ≥ 70% at screening visit.
11. At least 21 days have passed since completing radiotherapy at the time of randomization.
12. 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.
13. Has recovered from all therapy related toxicity to ≤ grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy).
14. Patient can tolerate a starting dose of docetaxel of 75 mg/M2 or cabazitaxel at 25 mg/M2.
15. Patient must have remained on the same bisphosphonate or denosumab usage for a minimum of 12 weeks prior to randomization.
16. Written informed consent must be obtained prior to any protocol-specific procedures being performed.

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. Life expectancy less than 12 weeks.
3. Previously participated in any clinical trial evaluating custirsen.
4. Received any other cytotoxic chemotherapy as a second-line treatment after first-line docetaxel-based therapy.
5. Not on any opioid analgesic regimen for their prostate cancer-related pain.
6. Receiving more than one drug within each of the separate categories of long-acting opioid, short-acting opioid, and non-opioid.
7. Receiving any analgesic specified in the protocol as unacceptable for this study.
8. Planned concomitant participation in another clinical trial of an experimental agent, vaccine or device. Concomitant participation in observational studies is acceptable.
9. Inability to communicate and read in English, Spanish or French.

Primary outcomes:
measure: To ascertain whether the investigational arm has a greater proportion of patients with durable pain palliation as compared to the control arm.
timeFrame: 3 to 6 months
Secondary outcomes:
measure: 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.
timeFrame: 6 months.
measure: Safety
timeFrame: 6 months
Other outcomes:
Locations:
city: La Verne
country: United States
state: California
city: Ft. Lauderdale
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Honolulu
country: United States
state: Hawaii
city: Urbana
country: United States
state: Illinois
city: Metairie
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Burlington
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Syracuse
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Columbia
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Tyler
country: United States
state: Texas
city: Winnipeg
country: Canada
state: Manitoba
city: Hamilton
country: Canada
state: Ontario
city: Lyon
country: France
city: Paris
country: France
city: Saint Herblain
country: France
city: Villejuif
country: France
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Sabadell
country: Spain
city: Valencia
country: Spain
city: Cambridge
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Oregon Health and Science University
name: Tomasz M Beer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Juravinski Cancer Centre, McMaster University
name: Sebastien J Hotte, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Gustave Roussy, University of Paris
name: Karim Fizazi, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: