AMG 386 (Trebananib) in Ovarian Cancer (TRINOVA-2)

Sponsor

Amgen (Industry)

Overall Status

Terminated

CT.gov ID

NCT01281254

Collaborator

(none)

223

Enrollment

106

Locations

Arms

Actual Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine if AMG 386 plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival (PFS)

The hypothesis for this study is that AMG 386 plus PLD will prolong PFS compared to placebo plus PLD in women with recurrent partially platinum sensitive or resistant epithelial ovarian, primary peritoneal or fallopian tube cancer.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cancer	Drug: AMG386 plus PLD Drug: Placebo plus PLD	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

223 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Double-Blind Trial of Pegylated Liposomal Doxorubicin (PLD) Plus AMG 386 or Placebo in Women With Recurrent Partially Platinum Sensitive or Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Actual Study Start Date :

Apr 18, 2011

Actual Primary Completion Date :

Aug 29, 2014

Actual Study Completion Date :

Apr 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo plus PLD Arm B: PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 placebo IV weekly (QW)	Drug: Placebo plus PLD Pegylated Liposomal Doxorubicin (Doxil/Caelyx) is a preparation of doxorubicin in a liposome that contains surface-grafted segments of the hydrophilic polymer methoxypolyethylene glycol associated with prolonged pharmacokinetics of the free drug. PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 placebo IV weekly (QW)
Experimental: AMG386 plus PLD Arm A: PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 15 mg/kg IV weekly (QW)	Drug: AMG386 plus PLD AMG 386 is a first in class investigational anti angiogenic drug that provides potent and selective inhibition of angiopoietins. AMG 386 is designed to inhibit angiogenesis by sequestering Ang1 and Ang2, thereby preventing their interaction with the Tie2 receptor. Pegylated Liposomal Doxorubicin (Doxil/Caelyx) is a preparation of doxorubicin in a liposome that contains surface-grafted segments of the hydrophilic polymer methoxypolyethylene glycol associated with prolonged pharmacokinetics of the free drug. PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 15 mg/kg IV weekly (QW)

Arm

Intervention/Treatment

Placebo Comparator: Placebo plus PLD

Arm B: PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 placebo IV weekly (QW)

Drug: Placebo plus PLD

Pegylated Liposomal Doxorubicin (Doxil/Caelyx) is a preparation of doxorubicin in a liposome that contains surface-grafted segments of the hydrophilic polymer methoxypolyethylene glycol associated with prolonged pharmacokinetics of the free drug. PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 placebo IV weekly (QW)

Experimental: AMG386 plus PLD

Arm A: PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 15 mg/kg IV weekly (QW)

Drug: AMG386 plus PLD

AMG 386 is a first in class investigational anti angiogenic drug that provides potent and selective inhibition of angiopoietins. AMG 386 is designed to inhibit angiogenesis by sequestering Ang1 and Ang2, thereby preventing their interaction with the Tie2 receptor. Pegylated Liposomal Doxorubicin (Doxil/Caelyx) is a preparation of doxorubicin in a liposome that contains surface-grafted segments of the hydrophilic polymer methoxypolyethylene glycol associated with prolonged pharmacokinetics of the free drug. PLD 50 mg/m2 IV every 4 weeks (Q4W) and blinded AMG 386 15 mg/kg IV weekly (QW)

Outcome Measures

Primary Outcome Measures

To determine if AMG 386 plus PLD is superior to placebo plus PLD as measured by progression-free survival, defined as the time from randomization to the earliest of the dates of first radiologic disease progression per RECIST 1.1 with modifications [Radiological imaging will be performed 8 weeks ± 1 week, starting from date of randomization for the first 64 weeks, then every 16 weeks ± 1 week for the next 32 weeks, and then every 24 weeks ± 4 weeks thereafter.]

Secondary Outcome Measures

• To determine if AMG 386 plus PLD is superior to placebo plus PLD as measured by overall survival [weekly]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically documented invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer
Radiographically documented disease progression either on or following the last dose of the prior regimen for epithelial ovarian, primary peritoneal, or fallopian tube cancer
Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound.
Female 18 years of age or older at the time the written informed consent is obtained
Adequate organ and hematological function

Exclusion Criteria:

Subjects who have received more than 3 previous regimens of anti cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer
Subjects treated with prior pegylated liposomal doxorubicin (PLD) or any anthracycline-based or mitoxantrone-based chemotherapy
Subjects with primary platinum-refractory disease
Subjects with platinum-free interval (PFI) > 12 months from their last platinum based therapy
History of central nervous system metastasis
Major surgery within 28 days prior to randomization or still recovering from prior surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90027
2	Research Site	San Francisco	California	United States	94143
3	Research Site	Norwalk	Connecticut	United States	06856
4	Research Site	Stamford	Connecticut	United States	06902
5	Research Site	Orlando	Florida	United States	32806
6	Research Site	Tampa	Florida	United States	33612
7	Research Site	Evanston	Illinois	United States	60201
8	Research Site	Saint Louis Park	Minnesota	United States	55426
9	Research Site	New York	New York	United States	10029
10	Research Site	Asheville	North Carolina	United States	28806
11	Research Site	Durham	North Carolina	United States	27710
12	Research Site	Winston-Salem	North Carolina	United States	27103
13	Research Site	Bismarck	North Dakota	United States	58501
14	Research Site	Abington	Pennsylvania	United States	19001
15	Research Site	Sioux Falls	South Dakota	United States	57104
16	Research Site	Fort Sam Houston	Texas	United States	78234
17	Research Site	San Antonio	Texas	United States	78229
18	Research Site	Annandale	Virginia	United States	22003
19	Research Site	Green Bay	Wisconsin	United States	54301
20	Research Site	Milwaukee	Wisconsin	United States	53215
21	Research Site	West Allis	Wisconsin	United States	53227
22	Research Site	New Lambton Heights	New South Wales	Australia	2305
23	Research Site	Wahroonga	New South Wales	Australia	2076
24	Research Site	Auchenflower	Queensland	Australia	4066
25	Research Site	Greenslopes	Queensland	Australia	4120
26	Research Site	East Bentleigh	Victoria	Australia	3165
27	Research Site	Footscray	Victoria	Australia	3011
28	Research Site	Malvern	Victoria	Australia	3144
29	Research Site	Parkville	Victoria	Australia	3052
30	Research Site	Graz		Austria	8020
31	Research Site	Graz		Austria	8036
32	Research Site	Innsbruck		Austria	6020
33	Research Site	Linz		Austria	4010
34	Research Site	Wien		Austria	1090
35	Research Site	Wien		Austria	1160
36	Research Site	Charleroi		Belgium	6000
37	Research Site	Edegem		Belgium	2650
38	Research Site	Gent		Belgium	9000
39	Research Site	Ieper		Belgium	8900
40	Research Site	Leuven		Belgium	3000
41	Research Site	Libramont		Belgium	6800
42	Research Site	Liège		Belgium	4000
43	Research Site	Namur		Belgium	5000
44	Research Site	London	Ontario	Canada	N6A 4L6
45	Research Site	Toronto	Ontario	Canada	M4N 3M5
46	Research Site	Toronto	Ontario	Canada	M5G 2M9
47	Research Site	Herlev		Denmark	2730
48	Research Site	København		Denmark	2100
49	Research Site	Amiens		France	80000
50	Research Site	Avignon cedex 9		France	84918
51	Research Site	Lyon cedex 8		France	69373
52	Research Site	Poitiers		France	86021
53	Research Site	Saint Cloud		France	92210
54	Research Site	Berlin		Germany	13353
55	Research Site	Bonn		Germany	53105
56	Research Site	Düsseldorf		Germany	40217
57	Research Site	Erlangen		Germany	91054
58	Research Site	Essen		Germany	45136
59	Research Site	Frankfurt am Main		Germany	60590
60	Research Site	Freiburg		Germany	79106
61	Research Site	Hannover		Germany	30177
62	Research Site	Marburg		Germany	35043
63	Research Site	München		Germany	81377
64	Research Site	München		Germany	81675
65	Research Site	Rostock		Germany	18059
66	Research Site	Tübingen		Germany	72076
67	Research Site	Hong Kong		Hong Kong
68	Research Site	New Territories		Hong Kong
69	Research Site	Budapest		Hungary	1032
70	Research Site	Budapest		Hungary	1062
71	Research Site	Debrecen		Hungary	4032
72	Research Site	Miskolc		Hungary	3526
73	Research Site	Szeged		Hungary	6720
74	Research Site	Zalaegerszeg - Pozva		Hungary	8900
75	Research Site	Campobasso		Italy	86100
76	Research Site	Genova		Italy	16128
77	Research Site	Milano		Italy	20133
78	Research Site	Milano		Italy	20141
79	Research Site	Napoli		Italy	80131
80	Research Site	Roma		Italy	00128
81	Research Site	Roma		Italy	00161
82	Research Site	Roma		Italy	00168
83	Research Site	Grafton, Auckland		New Zealand	1023
84	Research Site	Tauranga		New Zealand	3143
85	Research Site	Bialystok		Poland	15-027
86	Research Site	Gdansk		Poland	80-219
87	Research Site	Singapore		Singapore	169610
88	Research Site	Singapore		Singapore	229899
89	Research Site	Bratislava		Slovakia	812 50
90	Research Site	Bratislava		Slovakia	831 01
91	Research Site	Kosice		Slovakia	041 91
92	Research Site	Presov		Slovakia	080 01
93	Research Site	Aarau		Switzerland	5001
94	Research Site	Chur		Switzerland	7000
95	Research Site	Geneva 14		Switzerland	1211
96	Research Site	Zurich		Switzerland	8091
97	Research Site	Tainan		Taiwan	70403
98	Research Site	Taipei		Taiwan	10041
99	Research Site	Taipei		Taiwan	10449
100	Research Site	London		United Kingdom	NW1 2PG
101	Research Site	London		United Kingdom	SE1 9RT
102	Research Site	London		United Kingdom	SW3 6JJ
103	Research Site	Manchester		United Kingdom	M20 4BX
104	Research Site	Northwood		United Kingdom	HA6 2RN
105	Research Site	Nottingham		United Kingdom	NG5 1PB
106	Research Site	Poole		United Kingdom	BH15 2JB