Comparison of Cabazitaxel/Prednisone Alone or in Combination With Custirsen for 2nd Line Chemotherapy in Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT01578655
- Lead Sponsor
- Achieve Life Sciences
- Brief Summary
This Phase 3 study has been designed to confirm that adding custirsen to cabazitaxel/prednisone treatment can slow tumor progression and enhance survival outcomes compared to standard cabazitaxel/prednisone treatment in men with metastatic castrate resistant prostate cancer (CRPC). This will be a randomized, open-label, multicenter, international trial. Treatment will consist of cabazitaxel/prednisone/custirsen vs. cabazitaxel/prednisone. A total of approximately 630 patients will be randomized with equal probability to the two arms.
- Detailed Description
Until recently, options for second-line chemotherapy in CRPC have included docetaxel retreatment, mitoxantrone, or other chemotherapies, without proven clinical benefit. In 2010, a Phase 3 second-line chemotherapy trial (TROPIC) showed a survival advantage for cabazitaxel, a semi-synthetic taxane selected to overcome the emergence of taxane resistance, when compared to mitoxantrone.
Clusterin is a stress-activated cytoprotective chaperone up-regulated by a variety of anti-cancer therapies that confers treatment resistance when over-expressed. Inhibition of clusterin expression using custirsen has been shown to enhance tumor cell death following treatment with chemotherapy.
The clinical activity of custirsen in combination with the taxane docetaxel has been shown in two Phase 2 studies. Given the results observed using a taxane as either first-line or second-line chemotherapy in CRPC, combination with custirsen may decrease taxane resistance and enhance the survival benefit of taxane therapy. Thus, a combination of custirsen with cabazitaxel may further enhance survival in second-line taxane chemotherapy for CRPC.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 630
- Histological or cytological diagnosis of adenocarcinoma of the prostate
- Metastatic disease on chest, abdominal, or pelvic CT scan and/or bone scan
- Previous first-line treatment for CRPC with a docetaxel-containing regimen
- Current progressive disease
- Increasing serum PSA level (for patients who progress based only on increasing serum PSA level, a minimum starting value of 5.0 ng/mL is required)
- Baseline laboratory values as defined
- Willing to continue primary androgen suppression with gonadotropin-releasing hormone (GnRH) analogues (unless treated with bilateral orchiectomy)
- Karnofsky score ≥70%
- At least 21 days have passed since completing radiotherapy
- At least 21 days have passed since receiving any investigational agent at the time of randomization
- At least 21 days have passed since major surgery
- Recovered from any docetaxel therapy-related neuropathy to ≤grade 1 at the time of randomization
- Recovered from all therapy related toxicity to ≤grade 2 (except alopecia, anemia, and any signs or symptoms of androgen deprivation therapy) at the time of randomization
- Able to tolerate a starting dose of 25 mg/m² cabazitaxel
- Willing to not add, delete, or change current bisphosphonate or denosumab usage
- Able to tolerate oral prednisone at 10 mg per day
- Competent to provide written informed consent
- Received any other cytotoxic chemotherapy beyond the first-line docetaxel-containing regimen as treatment for prostate cancer
- Received prior radioisotope with strontium 89 or samarium 153
- Received any cycling, intermittent, or continuous hormonal treatment within 21 days prior to randomization with the exception of the continuous GnRH analogues (prior treatment with abiraterone or MDV3100 is allowed as long as 21 days have passed since last dose)
- Participated in a prior Phase 3 clinical study evaluating custirsen regardless of study arm assignment
- Requiring ongoing treatment during the study with medications known to be either strong CYP3A inhibitors or strong CYP3A inducers
- History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated
- Current symptomatic cord compression requiring surgery or radiation therapy
- Active second malignancy (except non melanomatous skin or superficial bladder cancer) defined in general as requiring anticancer therapy or at high risk of recurrence during the study
- Uncontrolled medical condition or significant concurrent illness that in the opinion of the Investigator would preclude protocol therapy
- Known severe hypersensitivity to taxanes or polysorbate 80-containing drugs
- Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cabazitaxel plus Custirsen custirsen sodium cabazitaxel, prednisone, and custirsen sodium Cabazitaxel plus Custirsen prednisone cabazitaxel, prednisone, and custirsen sodium Cabazitaxel plus Custirsen cabazitaxel cabazitaxel, prednisone, and custirsen sodium Cabazitaxel cabazitaxel cabazitaxel and prednisone Cabazitaxel prednisone cabazitaxel and prednisone
- Primary Outcome Measures
Name Time Method Survival in the intent-to-treat population 3.4 years To determine whether the survival for patients randomized to the investigational arm (cabazitaxel/prednisone plus custirsen) is consistent with longer survival as compared to patients randomized to the control arm (cabazitaxel/prednisone).
Survival in the poor-prognosis patient population 2.7 years To determine whether the survival for patients randomized to the investigational arm (cabazitaxel/prednisone plus custirsen) and identified as having poor prognosis is consistent with longer survival as compared to patients randomized to the control arm (cabazitaxel/prednisone) and identified as having poor prognosis.
- Secondary Outcome Measures
Name Time Method Progression-free survival at Day 140 From randomization to Day 125 to Day 155 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 defined as disease progression or death on or before Day 140.
Trial Locations
- Locations (93)
Georgia Cancer Specialists, P.C.
🇺🇸Marietta, Georgia, United States
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Krajská nemocnice Liberec a.s.
🇨🇿Liberec, Czech Republic
The Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
University Hospital Olomouc
🇨🇿Olomouc, Czech Republic
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Krajská nemo. T.Bati, a. s.
🇨🇿Zlín, Severomoravsky Kraj, Czech Republic
Cancer Research UK
🇬🇧Birmingham, England, United Kingdom
Christie Hospital NHS Foundation Trust
🇬🇧Manchester, England, United Kingdom
Nottingham City Hospital NHS Trust
🇬🇧Nottingham, England, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, England, United Kingdom
Cancer Centers of North Carolina
🇺🇸Raleigh, North Carolina, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Blumenthal Cancer Center
🇺🇸Charlotte, North Carolina, United States
R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health Oshawa
🇨🇦Oshawa, Ontario, Canada
The Mark H. Zangmeister Center
🇺🇸Columbus, Ohio, United States
Albert Einstein Medical Center
🇺🇸Bronx, New York, United States
The Center for Hematology-Oncology
🇺🇸Boca Raton, Florida, United States
Centre François Baclesse
🇫🇷Caen cedex 05, Basse-Normandie, France
Rocky Mountain Cancer Center
🇺🇸Boulder, Colorado, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Oncology Hematology Care, Inc.
🇺🇸Blue Ash, Ohio, United States
British Columbia Cancer Agency
🇨🇦Vancouver, British Columbia, Canada
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
London Health Sciences Center
🇨🇦London, Ontario, Canada
Hôpital Saint Louis
🇫🇷Paris, Ile de France, France
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
Cancer Centers of the Carolinas
🇺🇸Greenville, South Carolina, United States
St George Public Hospital
🇦🇺Kogarah, New South Wales, Australia
CHUM-Hospital Notre-Dame
🇨🇦Montréal, Quebec, Canada
Russian Research Center of Radiology
🇷🇺Moscow, Russian Federation
Centre Léon Bérard
🇫🇷Lyon cédex 08, Rhone-Alpes, France
Royal North Shore Hospital
🇦🇺Saint Leonards, New South Wales, Australia
Clatterbridge Centre for Oncology NHS Foundation Trust
🇬🇧Wirral, England, United Kingdom
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Cancer Research Center na NN Blokhin
🇷🇺Moscow, Russian Federation
Hertzen Rsrch Inst of Oncology
🇷🇺Moscow, Russian Federation
Urology Research Institute
🇷🇺Moscow, Russian Federation
Institut de Cancérologie de l'Ouest - René Gauducheau
🇫🇷Saint Herblain, Pays de la Loire, France
Stavropol Reg Oncology Ctr
🇷🇺Stavropol, Russian Federation
Sverdlovsk Reg Clin Hosp#1
🇷🇺Ekaterinburg, Ural, Russian Federation
The Royal Marsden Hospital
🇬🇧Surrey, England, United Kingdom
Institut Paoli Calmettes
🇫🇷Marseille, France
Volgograd Regional Oncological Dispensary
🇷🇺Volzhskiy, Volgograd, Russian Federation
State Healthcare Inst Omsk Reg
🇷🇺Omsk, Russian Federation
Saint Petersburg City Oncological Dispensary
🇷🇺Saint Petersburg, Russian Federation
Sharp Health Care
🇺🇸San Diego, California, United States
California Pacific Medical Center Research Institute
🇺🇸San Francisco, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Urology Cancer Center and GU Research Network
🇺🇸Omaha, Nebraska, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Prostate Oncology Specialists
🇺🇸Marina Del Rey, California, United States
Florida Cancer Specialists
🇺🇸Inverness, Florida, United States
Monter Cancer Center
🇺🇸Lake Success, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
The West Clinic
🇺🇸Memphis, Tennessee, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Fakultni nemo Hradec Králové
🇨🇿Hradec Králové, Czech Republic
Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie
🇫🇷Poitiers Cedex, Poitou-Charentes, France
Centre Antoine Lacassagne
🇫🇷Nice Cedex 2, Provence Alpes Cote d'Azur, France
Institut Curie
🇫🇷Paris Cedex 05, Ile-de-France, France
Szegedi Tudományegyetem, Onkoterápiás Klinika
🇭🇺Szeged, Csongrad, Hungary
S Inst Hlth Altay Reg Onc Disp
🇷🇺Barnaul, Russian Federation
Ivanovo Reg Oncology Centre
🇷🇺Ivanovo, Russian Federation
Petrov Research Oncology Institute
🇷🇺Saint Petersburg, Russian Federation
Addenbrookes Hospital Cambridge
🇬🇧Cambridge, England, United Kingdom
Beatson Cancer Centre, Glasgow
🇬🇧Glasgow, Scotland, United Kingdom
Haematology and Oncology Clinics of Australia
🇦🇺Brisbane, Queensland, Australia
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Chattanooga Oncology and Hematology Associates
🇺🇸Chattanooga, Tennessee, United States
South Carolina Oncology Associates
🇺🇸Columbia, South Carolina, United States
Texas Oncology, PA
🇺🇸Dallas, Texas, United States
Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Epworth Healthcare
🇦🇺Richmond, Victoria, Australia
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Institut Gustave Roussy
🇫🇷Villejuif, Ile-de-France, France
Pándy Kálmán Megyei Kórház
🇭🇺Gyula, Bekes, Hungary
Institut Jean-Godinot
🇫🇷Reims, Champagne-Ardenne, France
Országos Onkológiai Intézet
🇭🇺Budapest, Hungary
Semmelweis Egyetem Általános Orvostudományi Kar
🇭🇺Budapest, Hungary
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Smilow Cancer Hospital at Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
The Ottawa Hospital Regional Cancer Centre
🇨🇦Ottawa, Ontario, Canada
U of Surrey Post Grad Med
🇬🇧Guildford, England, United Kingdom