Comparison of Cabazitaxel/Prednisone Alone or in Combination With Custirsen for 2nd Line Chemotherapy in Prostate Cancer

Prostate Cancer Clinical Trial

— AFFINITY  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01578655
• Other study ID #: OGX-011-12
• Status: Completed
• Phase: Phase 3
• First received: April 9, 2012
• Last updated: October 11, 2016
• Start date: August 2012
• Est. completion date: July 2016

Study information

• Verified date: October 2016
• Source: OncoGenex Technologies
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 630
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• cabazitaxel
Cabazitaxel (25mg/m² IV) is administered on day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or completion of 10 cycles
• prednisone
Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles
• custirsen sodium
Custirsen is administered as 3 loading doses (640 mg IV each) within 9 days, followed by weekly custirsen (640 mg IV) during each 21-day cycle until disease progression, unacceptable toxicity, or completion of 10 cycles

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Haematology and Oncology Clinics of Australia	Brisbane	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	The Canberra Hospital	Garran	Australian Capital Territory
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	St George Public Hospital	Kogarah	New South Wales
Australia	Epworth Healthcare	Richmond	Victoria
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Center	London	Ontario
Canada	CHUM-Hospital Notre-Dame	Montréal	Quebec
Canada	R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health Oshawa	Oshawa	Ontario
Canada	The Ottawa Hospital Regional Cancer Centre	Ottawa	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
Czech Republic	Fakultni nemo Hradec Králové	Hradec Králové
Czech Republic	Krajská nemocnice Liberec a.s.	Liberec
Czech Republic	University Hospital Olomouc	Olomouc
Czech Republic	Krajská nemo. T.Bati, a. s.	Zlín	Severomoravsky Kraj
France	Centre François Baclesse	Caen cedex 05	Basse-Normandie
France	Centre Léon Bérard	Lyon cédex 08	Rhone-Alpes
France	Institut Paoli Calmettes	Marseille
France	Centre Antoine Lacassagne	Nice Cedex 2	Provence Alpes Cote d'Azur
France	Hôpital Saint Louis	Paris	Ile de France
France	Institut Curie	Paris Cedex 05	Ile-de-France
France	Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie	Poitiers Cedex	Poitou-Charentes
France	Institut Jean-Godinot	Reims	Champagne-Ardenne
France	Institut de Cancérologie de l'Ouest - René Gauducheau	Saint Herblain	Pays de la Loire
France	Institut Gustave Roussy	Villejuif	Ile-de-France
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Semmelweis Egyetem Általános Orvostudományi Kar	Budapest
Hungary	Pándy Kálmán Megyei Kórház	Gyula	Bekes
Hungary	Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház	Miskolc	Borsod-Abauj-Zemplen
Hungary	Szegedi Tudományegyetem, Onkoterápiás Klinika	Szeged	Csongrad
Russian Federation	S Inst Hlth Altay Reg Onc Disp	Barnaul
Russian Federation	Sverdlovsk Reg Clin Hosp#1	Ekaterinburg	Ural
Russian Federation	Ivanovo Reg Oncology Centre	Ivanovo
Russian Federation	Cancer Research Center na NN Blokhin	Moscow
Russian Federation	Hertzen Rsrch Inst of Oncology	Moscow
Russian Federation	Russian Research Center of Radiology	Moscow
Russian Federation	Urology Research Institute	Moscow
Russian Federation	State Healthcare Inst Omsk Reg	Omsk
Russian Federation	Petrov Research Oncology Institute	Saint Petersburg
Russian Federation	Saint Petersburg City Oncological Dispensary	Saint Petersburg
Russian Federation	Stavropol Reg Oncology Ctr	Stavropol
Russian Federation	Volgograd Regional Oncological Dispensary	Volzhskiy	Volgograd
United Kingdom	Cancer Research UK	Birmingham	England
United Kingdom	Addenbrookes Hospital Cambridge	Cambridge	England
United Kingdom	Beatson Cancer Centre, Glasgow	Glasgow	Scotland
United Kingdom	U of Surrey Post Grad Med	Guildford	England
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	The Royal Marsden Hospital	Surrey	England
United Kingdom	Musgrove Park Hospital	Taunton	England
United Kingdom	Clatterbridge Centre for Oncology NHS Foundation Trust	Wirral	England
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Oncology Hematology Care, Inc.	Blue Ash	Ohio
United States	The Center for Hematology-Oncology	Boca Raton	Florida
United States	Boston University Medical Center	Boston	Massachusetts
United States	Rocky Mountain Cancer Center	Boulder	Colorado
United States	Albert Einstein Medical Center	Bronx	New York
United States	Blumenthal Cancer Center	Charlotte	North Carolina
United States	Chattanooga Oncology and Hematology Associates	Chattanooga	Tennessee
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	The Mark H. Zangmeister Center	Columbus	Ohio
United States	Texas Oncology, PA	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Florida Cancer Specialists	Inverness	Florida
United States	Monter Cancer Center	Lake Success	New York
United States	Georgia Cancer Specialists, P.C.	Marietta	Georgia
United States	Prostate Oncology Specialists	Marina Del Rey	California
United States	The West Clinic	Memphis	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Smilow Cancer Hospital at Yale New Haven Hospital	New Haven	Connecticut
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Urology Cancer Center and GU Research Network	Omaha	Nebraska
United States	Oregon Health and Science University	Portland	Oregon
United States	Cancer Centers of North Carolina	Raleigh	North Carolina
United States	Virginia Cancer Institute	Richmond	Virginia
United States	University of California Davis Medical Center	Sacramento	California
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Sharp Health Care	San Diego	California
United States	California Pacific Medical Center Research Institute	San Francisco	California
United States	Washington University School of Medicine	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
OncoGenex Technologies

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czech Republic,  France,  Hungary,  Russian Federation,  United Kingdom, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival in the intent-to-treat population	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).	3.4 years	No
Primary	Survival in the poor-prognosis patient population	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.	2.7 years	No
Secondary	Progression-free survival at Day 140	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.	From randomization to Day 125 to Day 155	No