Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01281254




Registration number
NCT01281254
Ethics application status
Date submitted
20/01/2011
Date registered
21/01/2011
Date last updated
2/12/2017

Titles & IDs
Public title
AMG 386 (Trebananib) in Ovarian Cancer (TRINOVA-2)
Scientific 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
Secondary ID [1] 0 0
2009-017946-30
Secondary ID [2] 0 0
20060517
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fallopian Tube Cancer 0 0
Ovarian Cancer 0 0
Primary Peritoneal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG386 plus PLD
Treatment: Drugs - Placebo plus PLD

Placebo Comparator: Placebo plus PLD - Arm B: 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)


Treatment: Drugs: 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)

Treatment: Drugs: 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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
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 [1] 0 0
• To determine if AMG 386 plus PLD is superior to placebo plus PLD as measured by overall survival
Timepoint [1] 0 0
weekly

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/04/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/04/2017
Sample size
Target
Accrual to date
Final
223
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Research Site - New Lambton Heights
Recruitment hospital [2] 0 0
Research Site - Wahroonga
Recruitment hospital [3] 0 0
Research Site - Auchenflower
Recruitment hospital [4] 0 0
Research Site - Greenslopes
Recruitment hospital [5] 0 0
Research Site - East Bentleigh
Recruitment hospital [6] 0 0
Research Site - Footscray
Recruitment hospital [7] 0 0
Research Site - Malvern
Recruitment hospital [8] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 0 0
2076 - Wahroonga
Recruitment postcode(s) [3] 0 0
4066 - Auchenflower
Recruitment postcode(s) [4] 0 0
4120 - Greenslopes
Recruitment postcode(s) [5] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [6] 0 0
3011 - Footscray
Recruitment postcode(s) [7] 0 0
3144 - Malvern
Recruitment postcode(s) [8] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
North Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Austria
State/province [14] 0 0
Graz
Country [15] 0 0
Austria
State/province [15] 0 0
Innsbruck
Country [16] 0 0
Austria
State/province [16] 0 0
Linz
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Charleroi
Country [19] 0 0
Belgium
State/province [19] 0 0
Edegem
Country [20] 0 0
Belgium
State/province [20] 0 0
Gent
Country [21] 0 0
Belgium
State/province [21] 0 0
Ieper
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Belgium
State/province [23] 0 0
Libramont
Country [24] 0 0
Belgium
State/province [24] 0 0
Liège
Country [25] 0 0
Belgium
State/province [25] 0 0
Namur
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Denmark
State/province [27] 0 0
Herlev
Country [28] 0 0
Denmark
State/province [28] 0 0
København
Country [29] 0 0
France
State/province [29] 0 0
Amiens
Country [30] 0 0
France
State/province [30] 0 0
Avignon cedex 9
Country [31] 0 0
France
State/province [31] 0 0
Lyon cedex 8
Country [32] 0 0
France
State/province [32] 0 0
Poitiers
Country [33] 0 0
France
State/province [33] 0 0
Saint Cloud
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
Country [35] 0 0
Germany
State/province [35] 0 0
Bonn
Country [36] 0 0
Germany
State/province [36] 0 0
Düsseldorf
Country [37] 0 0
Germany
State/province [37] 0 0
Erlangen
Country [38] 0 0
Germany
State/province [38] 0 0
Essen
Country [39] 0 0
Germany
State/province [39] 0 0
Frankfurt am Main
Country [40] 0 0
Germany
State/province [40] 0 0
Freiburg
Country [41] 0 0
Germany
State/province [41] 0 0
Hannover
Country [42] 0 0
Germany
State/province [42] 0 0
Marburg
Country [43] 0 0
Germany
State/province [43] 0 0
München
Country [44] 0 0
Germany
State/province [44] 0 0
Rostock
Country [45] 0 0
Germany
State/province [45] 0 0
Tübingen
Country [46] 0 0
Hong Kong
State/province [46] 0 0
Hong Kong
Country [47] 0 0
Hong Kong
State/province [47] 0 0
New Territories
Country [48] 0 0
Hungary
State/province [48] 0 0
Budapest
Country [49] 0 0
Hungary
State/province [49] 0 0
Debrecen
Country [50] 0 0
Hungary
State/province [50] 0 0
Miskolc
Country [51] 0 0
Hungary
State/province [51] 0 0
Szeged
Country [52] 0 0
Hungary
State/province [52] 0 0
Zalaegerszeg - Pozva
Country [53] 0 0
Italy
State/province [53] 0 0
Campobasso
Country [54] 0 0
Italy
State/province [54] 0 0
Genova
Country [55] 0 0
Italy
State/province [55] 0 0
Milano
Country [56] 0 0
Italy
State/province [56] 0 0
Napoli
Country [57] 0 0
Italy
State/province [57] 0 0
Roma
Country [58] 0 0
New Zealand
State/province [58] 0 0
Grafton, Auckland
Country [59] 0 0
New Zealand
State/province [59] 0 0
Tauranga
Country [60] 0 0
Poland
State/province [60] 0 0
Bialystok
Country [61] 0 0
Poland
State/province [61] 0 0
Gdansk
Country [62] 0 0
Singapore
State/province [62] 0 0
Singapore
Country [63] 0 0
Slovakia
State/province [63] 0 0
Bratislava
Country [64] 0 0
Slovakia
State/province [64] 0 0
Kosice
Country [65] 0 0
Slovakia
State/province [65] 0 0
Presov
Country [66] 0 0
Switzerland
State/province [66] 0 0
Aarau
Country [67] 0 0
Switzerland
State/province [67] 0 0
Chur
Country [68] 0 0
Switzerland
State/province [68] 0 0
Geneva 14
Country [69] 0 0
Switzerland
State/province [69] 0 0
Zurich
Country [70] 0 0
Taiwan
State/province [70] 0 0
Tainan
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taipei
Country [72] 0 0
United Kingdom
State/province [72] 0 0
London
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Manchester
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Northwood
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Nottingham
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Poole

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01281254
Trial related presentations / publications
Marth C, Vergote I, Scambia G, Oberaigner W, Clamp A, Berger R, Kurzeder C, Colombo N, Vuylsteke P, Lorusso D, Hall M, Renard V, Pignata S, Kristeleit R, Altintas S, Rustin G, Wenham RM, Mirza MR, Fong PC, Oza A, Monk BJ, Ma H, Vogl FD, Bach BA. ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer. Eur J Cancer. 2017 Jan;70:111-121. doi: 10.1016/j.ejca.2016.09.004. Epub 2016 Dec 1.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01281254