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

Sponsor

Achieve Life Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01578655

Collaborator

(none)

630

Enrollment

Locations

Arms

Duration (Months)

6.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: cabazitaxel Drug: prednisone Drug: custirsen sodium	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

630 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2012

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cabazitaxel plus Custirsen cabazitaxel, prednisone, and custirsen sodium	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 Drug: prednisone Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles Drug: 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 Other Names: OGX-011 TV-1011
Active Comparator: Cabazitaxel cabazitaxel and prednisone	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 Drug: prednisone Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles

Arm

Intervention/Treatment

Experimental: Cabazitaxel plus Custirsen

cabazitaxel, prednisone, and custirsen sodium

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

Drug: prednisone

Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles

Drug: 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

Other Names:

OGX-011

TV-1011

Active Comparator: Cabazitaxel

cabazitaxel and prednisone

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

Drug: prednisone

Prednisone (10 mg PO) is administered daily until disease progression, unacceptable toxicity, or completion of 10 cycles

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country
1	Prostate Oncology Specialists	Marina Del Rey	California	United States
2	University of California Davis Medical Center	Sacramento	California	United States
3	Sharp Health Care	San Diego	California	United States
4	California Pacific Medical Center Research Institute	San Francisco	California	United States
5	Rocky Mountain Cancer Center	Boulder	Colorado	United States
6	Hartford Hospital	Hartford	Connecticut	United States
7	Smilow Cancer Hospital at Yale New Haven Hospital	New Haven	Connecticut	United States
8	The Center for Hematology-Oncology	Boca Raton	Florida	United States
9	Florida Cancer Specialists	Fort Myers	Florida	United States
10	Florida Cancer Specialists	Inverness	Florida	United States
11	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States
12	Georgia Cancer Specialists, P.C.	Marietta	Georgia	United States
13	Cancer Center of Kansas	Wichita	Kansas	United States
14	Boston University Medical Center	Boston	Massachusetts	United States
15	University of Michigan Health System	Ann Arbor	Michigan	United States
16	Karmanos Cancer Institute	Detroit	Michigan	United States
17	Washington University School of Medicine	St. Louis	Missouri	United States
18	Urology Cancer Center and GU Research Network	Omaha	Nebraska	United States
19	Albert Einstein Medical Center	Bronx	New York	United States
20	Monter Cancer Center	Lake Success	New York	United States
21	SUNY Upstate Medical University	Syracuse	New York	United States
22	Blumenthal Cancer Center	Charlotte	North Carolina	United States
23	Cancer Centers of North Carolina	Raleigh	North Carolina	United States
24	Oncology Hematology Care, Inc.	Blue Ash	Ohio	United States
25	The Mark H. Zangmeister Center	Columbus	Ohio	United States
26	Oregon Health and Science University	Portland	Oregon	United States
27	South Carolina Oncology Associates	Columbia	South Carolina	United States
28	Cancer Centers of the Carolinas	Greenville	South Carolina	United States
29	Chattanooga Oncology and Hematology Associates	Chattanooga	Tennessee	United States
30	The West Clinic	Memphis	Tennessee	United States
31	Tennessee Oncology, PLLC	Nashville	Tennessee	United States
32	Texas Oncology, PA	Dallas	Texas	United States
33	Utah Cancer Specialists	Salt Lake City	Utah	United States
34	Virginia Oncology Associates	Norfolk	Virginia	United States
35	Virginia Cancer Institute	Richmond	Virginia	United States
36	The Canberra Hospital	Garran	Australian Capital Territory	Australia
37	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia
38	St George Public Hospital	Kogarah	New South Wales	Australia
39	Royal North Shore Hospital	Saint Leonards	New South Wales	Australia
40	Westmead Hospital	Westmead	New South Wales	Australia
41	Haematology and Oncology Clinics of Australia	Brisbane	Queensland	Australia
42	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia
43	Royal Hobart Hospital	Hobart	Tasmania	Australia
44	Box Hill Hospital	Box Hill	Victoria	Australia
45	Austin Health	Heidelberg	Victoria	Australia
46	Epworth Healthcare	Richmond	Victoria	Australia
47	Cross Cancer Institute	Edmonton	Alberta	Canada
48	British Columbia Cancer Agency	Vancouver	British Columbia	Canada
49	Juravinski Cancer Centre	Hamilton	Ontario	Canada
50	London Health Sciences Center	London	Ontario	Canada
51	R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health Oshawa	Oshawa	Ontario	Canada
52	The Ottawa Hospital Regional Cancer Centre	Ottawa	Ontario	Canada
53	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada
54	CHUM-Hospital Notre-Dame	Montréal	Quebec	Canada
55	Krajská nemo. T.Bati, a. s.	Zlín	Severomoravsky Kraj	Czech Republic
56	Fakultni nemo Hradec Králové	Hradec Králové		Czech Republic
57	Krajská nemocnice Liberec a.s.	Liberec		Czech Republic
58	University Hospital Olomouc	Olomouc		Czech Republic
59	Centre François Baclesse	Caen cedex 05	Basse-Normandie	France
60	Institut Jean-Godinot	Reims	Champagne-Ardenne	France
61	Hôpital Saint Louis	Paris	Ile de France	France
62	Institut Curie	Paris Cedex 05	Ile-de-France	France
63	Institut Gustave Roussy	Villejuif	Ile-de-France	France
64	Institut de Cancérologie de l'Ouest - René Gauducheau	Saint Herblain	Pays de la Loire	France
65	Centre Hospitalier Universitaire de Poitiers Hôpital de la Milétrie	Poitiers Cedex	Poitou-Charentes	France
66	Centre Antoine Lacassagne	Nice Cedex 2	Provence Alpes Cote d'Azur	France
67	Centre Léon Bérard	Lyon cédex 08	Rhone-Alpes	France
68	Institut Paoli Calmettes	Marseille		France
69	Pándy Kálmán Megyei Kórház	Gyula	Bekes	Hungary
70	Borsod Abaúj Zemplén Megyei Kórház és Egyetemi Oktató Kórház	Miskolc	Borsod-Abauj-Zemplen	Hungary
71	Szegedi Tudományegyetem, Onkoterápiás Klinika	Szeged	Csongrad	Hungary
72	Országos Onkológiai Intézet	Budapest		Hungary
73	Semmelweis Egyetem Általános Orvostudományi Kar	Budapest		Hungary
74	Sverdlovsk Reg Clin Hosp#1	Ekaterinburg	Ural	Russian Federation
75	Volgograd Regional Oncological Dispensary	Volzhskiy	Volgograd	Russian Federation
76	S Inst Hlth Altay Reg Onc Disp	Barnaul		Russian Federation
77	Ivanovo Reg Oncology Centre	Ivanovo		Russian Federation
78	Cancer Research Center na NN Blokhin	Moscow		Russian Federation
79	Hertzen Rsrch Inst of Oncology	Moscow		Russian Federation
80	Russian Research Center of Radiology	Moscow		Russian Federation
81	Urology Research Institute	Moscow		Russian Federation
82	State Healthcare Inst Omsk Reg	Omsk		Russian Federation
83	Petrov Research Oncology Institute	Saint Petersburg		Russian Federation
84	Saint Petersburg City Oncological Dispensary	Saint Petersburg		Russian Federation
85	Stavropol Reg Oncology Ctr	Stavropol		Russian Federation
86	Cancer Research UK	Birmingham	England	United Kingdom
87	Addenbrookes Hospital Cambridge	Cambridge	England	United Kingdom
88	U of Surrey Post Grad Med	Guildford	England	United Kingdom
89	Christie Hospital NHS Foundation Trust	Manchester	England	United Kingdom
90	Nottingham City Hospital NHS Trust	Nottingham	England	United Kingdom
91	The Royal Marsden Hospital	Surrey	England	United Kingdom
92	Musgrove Park Hospital	Taunton	England	United Kingdom
93	Clatterbridge Centre for Oncology NHS Foundation Trust	Wirral	England	United Kingdom
94	Beatson Cancer Centre, Glasgow	Glasgow	Scotland	United Kingdom

Sponsors and Collaborators

Achieve Life Sciences

Investigators

Principal Investigator: Thomasz Beer, MD, Oregon Health & Science University, Portland, Oregon
Principal Investigator: Karim Fazazi, MD, Gustave Roussy Cancer Institute, University of Paris, France
Principal Investigator: Sebastien Hotte, MD, Juravinski Cancer Centre, Hamilton, Ontario, Canada