Clinical trial NCT01578655: Comparison of Cabazitaxel/Prednisone Alone or in Combination With Custirsen for 2nd Line Chemotherapy in Prostate Cancer
Official title: A Randomized Phase 3 Study Comparing Cabazitaxel/Prednisone in Combination With Custirsen (OGX-011) to Cabazitaxel/Prednisone for Second-Line Chemotherapy in Men With Metastatic Castrate Resistant Prostate Cancer (AFFINITY)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: custirsen sodium
prostate cancer
metastatic castrate resistant prostate cancer
overall survival
Lead sponsor: Achieve Life Sciences
Sponsor class: INDUSTRY
First posted: 2012-04-17
Enrollment: 630
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Survival in the intent-to-treat population
timeFrame: 3.4 years
measure: Survival in the poor-prognosis patient population
timeFrame: 2.7 years
Secondary outcomes:
measure: Progression-free survival at Day 140
timeFrame: From randomization to Day 125 to Day 155
Other outcomes:
Locations:
city: Marina Del Rey
country: United States
facility: Prostate Oncology Specialists
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Health Care
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven Hospital
state: Connecticut
city: Boca Raton
country: United States
facility: The Center for Hematology-Oncology
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Inverness
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Marietta
country: United States
facility: Georgia Cancer Specialists, P.C.
state: Georgia
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Urology Cancer Center and GU Research Network
state: Nebraska
city: Bronx
country: United States
facility: Albert Einstein Medical Center
state: New York
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center
state: North Carolina
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina
state: North Carolina
city: Blue Ash
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Columbus
country: United States
facility: The Mark H. Zangmeister Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Associates
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, PA
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Public Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Haematology and Oncology Clinics of Australia
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Richmond
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Oshawa
country: Canada
facility: R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: CHUM-Hospital Notre-Dame
state: Quebec
city: Zlín
country: Czech Republic
facility: Krajská nemo. T.Bati, a. s.
state: Severomoravsky Kraj
city: Hradec Králové
country: Czech Republic
facility: Fakultni nemo Hradec Králové
city: Liberec
country: Czech Republic
facility: Krajská nemocnice Liberec a.s.
city: Olomouc
country: Czech Republic
facility: University Hospital Olomouc
city: Caen cedex 05
country: France
facility: Centre François Baclesse
state: Basse-Normandie
city: Reims
country: France
facility: Institut Jean-Godinot
state: Champagne-Ardenne
city: Paris
country: France
facility: Hôpital Saint Louis
state: Ile de France
city: Paris Cedex 05
country: France
facility: Institut Curie
state: Ile-de-France
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Ile-de-France
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest - René Gauducheau
state: Pays de la Loire
city: Poitiers Cedex
country: France
facility: Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie
state: Poitou-Charentes
city: Nice Cedex 2
country: France
facility: Centre Antoine Lacassagne
state: Provence Alpes Cote d'Azur
city: Lyon cédex 08
country: France
facility: Centre Léon Bérard
state: Rhone-Alpes
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Gyula
country: Hungary
facility: Pándy Kálmán Megyei Kórház
state: Bekes
city: Miskolc
country: Hungary
facility: Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház
state: Borsod-Abauj-Zemplen
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem, Onkoterápiás Klinika
state: Csongrad
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Általános Orvostudományi Kar
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Reg Clin Hosp#1
state: Ural
city: Volzhskiy
country: Russian Federation
facility: Volgograd Regional Oncological Dispensary
state: Volgograd
city: Barnaul
country: Russian Federation
facility: S Inst Hlth Altay Reg Onc Disp
city: Ivanovo
country: Russian Federation
facility: Ivanovo Reg Oncology Centre
city: Moscow
country: Russian Federation
facility: Cancer Research Center na NN Blokhin
city: Moscow
country: Russian Federation
facility: Hertzen Rsrch Inst of Oncology
city: Moscow
country: Russian Federation
facility: Russian Research Center of Radiology
city: Moscow
country: Russian Federation
facility: Urology Research Institute
city: Omsk
country: Russian Federation
facility: State Healthcare Inst Omsk Reg
city: Saint Petersburg
country: Russian Federation
facility: Petrov Research Oncology Institute
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg City Oncological Dispensary
city: Stavropol
country: Russian Federation
facility: Stavropol Reg Oncology Ctr
city: Birmingham
country: United Kingdom
facility: Cancer Research UK
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital Cambridge
state: England
city: Guildford
country: United Kingdom
facility: U of Surrey Post Grad Med
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Surrey
country: United Kingdom
facility: The Royal Marsden Hospital
state: England
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
state: England
city: Wirral
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Foundation Trust
state: England
city: Glasgow
country: United Kingdom
facility: Beatson Cancer Centre, Glasgow
state: Scotland
Study officials:
affiliation: Oregon Health & Science University, Portland, Oregon
name: Thomasz Beer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gustave Roussy Cancer Institute, University of Paris, France
name: Karim Fazazi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Juravinski Cancer Centre, Hamilton, Ontario, Canada
name: Sebastien Hotte, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saad F, Hotte S, North S, Eigl B, Chi K, Czaykowski P, Wood L, Pollak M, Berry S, Lattouf JB, Mukherjee SD, Gleave M, Winquist E; Canadian Uro-Oncology Group. Randomized phase II trial of Custirsen (OGX-011) in combination with docetaxel or mitoxantrone as second-line therapy in patients with metastatic castrate-resistant prostate cancer progressing after first-line docetaxel: CUOG trial P-06c. Clin Cancer Res. 2011 Sep 1;17(17):5765-73. doi: 10.1158/1078-0432.CCR-11-0859. Epub 2011 Jul 25.
citation: Chi KN, Hotte SJ, Yu EY, Tu D, Eigl BJ, Tannock I, Saad F, North S, Powers J, Gleave ME, Eisenhauer EA. Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2010 Sep 20;28(27):4247-54. doi: 10.1200/JCO.2009.26.8771. Epub 2010 Aug 23.
citation: Beer TM, Hotte SJ, Saad F, Alekseev B, Matveev V, Flechon A, Gravis G, Joly F, Chi KN, Malik Z, Blumenstein B, Stewart PS, Jacobs CA, Fizazi K. Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1532-1542. doi: 10.1016/S1470-2045(17)30605-8. Epub 2017 Oct 9.