Clinical trial NCT01204749: TRINOVA-1: A Study of AMG 386 or Placebo, in Combination With Weekly Paclitaxel Chemotherapy, as Treatment for Ovarian Cancer, Primary Peritoneal Cancer and Fallopian Tube Cancer
Official title: A Phase 3, Randomized, Double-Blind Trial of Weekly Paclitaxel Plus AMG 386 or Placebo in Women With Recurrent Partially Platinum Sensitive or Resistant Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cancer
Keywords: AMGEN
AMG 386
Angiogenesis Inhibitors
Fallopian Tube Cancer
Primary Peritoneal Cancer
Paclitaxel
Ovarian Cancer
TRINOVA-1
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-09-17
Enrollment: 919
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if treatment with paclitaxel plus AMG 386 is superior to paclitaxel plus placebo in women with recurrent partially platinum sensitive or resistant epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.

AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.


Eligibility criteria: Inclusion Criteria:

* Female 18 years of age or older at the time the written informed consent is obtained
* Gynecologic Oncology Group (GOG) Performance Status of 0 or 1
* Life expectancy \>= 3 months (per investigator opinion)
* Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (Subjects with pseudomyxoma , mesothelioma, unknown primary tumor, sarcoma, or neuroendocrine histology, with borderline ovarian cancer, ie, subjects with low malignant potential tumors, and with clear cell or mucinous histology are excluded)
* Subjects must have undergone surgery for ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including at least a unilateral oophorectomy
* Radiologically evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with modifications
* Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation therapy, bevacizumab or extended therapy administered after surgical or non-surgical assessment.
* Adequate organ and hematological function
* Generally well controlled blood pressure with systolic blood pressure \<= 140 mmHg and diastolic blood pressure \<= 90 mmHg prior to randomization. The use of anti-hypertensive medications to control hypertension is permitted
* Radiographically documented disease progression either on or following the last dose of prior chemotherapy regimen for epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

Exclusion Criteria:

* Subjects who have received more than 3 previous regimens of anti-cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancers
* Subjects who have received paclitaxel as consolidation therapy, maintenance, or monotherapy are excluded
* Subjects with primary platinum-refractory disease
* Subjects with platinum-free interval (PFI) \> 12 months from their last platinum based therapy
* Radiotherapy \<= 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities
* Previous abdominal or pelvic radiotherapy
* History of arterial or venous thromboembolism within 12 months prior to randomization
* History of clinically significant bleeding within 6 months prior to randomization
* History of central nervous system metastasis
* Has not yet completed a 21 day washout period prior to randomization for any previous anti cancer systemic therapies (30 days for prior bevacizumab)
* Enrolled in or has not yet completed at least 30 days (prior to randomization) since ending other investigational device or drug, or currently receiving other investigational treatments
* Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 \>= Grade 2 in severity except alopecia
* Known active or ongoing infection (except uncomplicated urinary tract infection \[UTI\]) within 14 days prior to randomization
* Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
* Treatment within 30 days prior to randomization with strong immune modulators including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, and lenalidomide
* Clinically significant cardiovascular disease within 12 months prior to randomization
* Major surgery within 28 days prior to randomization or still recovering from prior surgery
* Minor surgical procedures, except placement of tunneled central venous access device within 3 days prior to randomization. Diagnostic laparoscopy is regarded as a minor surgical procedure.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: 8 Months on average
Secondary outcomes:
measure: Overall survival
timeFrame: 20 months on average
measure: Objective Response Rate
timeFrame: From Baseline (if subject has Measurable Disease) until objective response (radiologic)
measure: Duration of response
timeFrame: From Baseline until progression
measure: CA-125 response rate per Gynecologic Cancer Intergroup (GCIG) and change in CA-125
timeFrame: From Baseline until CA-125 response
measure: Incidence of adverse events and significant laboratory abnormalities
timeFrame: 8 Months on average
measure: Pharmacokinetics of AMG 386 (Cmax and Cmin)
timeFrame: Week 1 until week 9 of treatment
measure: Incidence of the occurrence of anti-AMG 386 antibody formation
timeFrame: Week 1 until maximum of 1-year following last dose of study drug
measure: Patient reported Health Related Quality of Life (HRQOL) and ovarian cancer related symptoms using Functional Assessment of Cancer Therapy - Ovary questionnaire (FACT-O)
timeFrame: From week 1 until 30-days following last study drug administration
measure: Overall health status using EuroQOL(EQ-5D)
timeFrame: From week 1 until 30-days following last study drug administration
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Diego
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state: California
city: Stanford
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state: California
city: Englewood
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state: Colorado
city: Danbury
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state: Connecticut
city: New Haven
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state: Connecticut
city: Hollywood
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state: Florida
city: Orlando
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state: Florida
city: Honolulu
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state: Hawaii
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city: Boston
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state: Massachusetts
city: Lebanon
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state: New Hampshire
city: Hackensack
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facility: Research Site
state: New Jersey
city: Brightwaters
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state: New York
city: New York
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state: New York
city: New York
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facility: Research Site
state: New York
city: Charlotte
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facility: Research Site
state: North Carolina
city: Charlotte
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state: North Carolina
city: Winston Salem
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state: North Carolina
city: Abington
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state: Pennsylvania
city: Chattanooga
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state: Utah
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city: Milwaukee
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city: Greenslopes
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state: Queensland
city: Bendigo
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state: Victoria
city: Bentleigh East
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facility: Research Site
state: Victoria
city: Footscray
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state: Victoria
city: Malvern
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facility: Research Site
state: Victoria
city: Parkville
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state: Victoria
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city: Leuven
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city: Namur
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city: Porto Alegre
country: Brazil
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state: Rio Grande do Sul
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city: ItajaÃ-
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state: Santa Catarina
city: Ribeirao Preto
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state: SÃ£o Paulo
city: Rio de Janeiro
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city: SÃ£o Paulo
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city: Gabrovo
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city: Plovdiv
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Stara Zagora
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city: Varna
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city: Calgary
country: Canada
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state: Alberta
city: Vancouver
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facility: Research Site
state: British Columbia
city: London
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state: Ontario
city: Toronto
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state: Ontario
city: Toronto
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facility: Research Site
state: Ontario
city: Montreal
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facility: Research Site
state: Quebec
city: Sherbrooke
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state: Quebec
city: Quebec
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facility: Research Site
city: Temuco
country: Chile
facility: Research Site
state: CautÃ-n
city: Valparaiso
country: Chile
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state: ValparaÃ-so
city: Zagreb
country: Croatia
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city: Brno
country: Czech Republic
facility: Research Site
city: Brno
country: Czech Republic
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Praha 5
country: Czech Republic
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city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Amiens
country: France
facility: Research Site
city: Angers
country: France
facility: Research Site
city: Avignon Cedex 2
country: France
facility: Research Site
city: Bayonne
country: France
facility: Research Site
city: Besancon Cedex
country: France
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Brest Cedex 2
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Le Mans
country: France
facility: Research Site
city: Lille Cedex
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille cedex 05
country: France
facility: Research Site
city: Marseille Cedex 09
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier Cedex 5
country: France
facility: Research Site
city: Nancy
country: France
facility: Research Site
city: Nantes Cedex 2
country: France
facility: Research Site
city: Nice cedex 2
country: France
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city: OrlÃ©ans cedex 2
country: France
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city: Paris cedex 15
country: France
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city: PÃ©rigueux cedex
country: France
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city: Reims Cedex
country: France
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city: Saint GrÃ©goire cedex
country: France
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city: Saint Herblain
country: France
facility: Research Site
city: Strasbourg
country: France
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city: Villejuif cedex
country: France
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city: Athens
country: Greece
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city: Heraklion
country: Greece
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city: Larissa
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city: Patra
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city: Thessaloniki
country: Greece
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city: Hong Kong
country: Hong Kong
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city: Hyderabad
country: India
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state: Andhra Pradesh
city: Mumbai
country: India
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state: Maharashtra
city: Nashik
country: India
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state: Maharashtra
city: Pune
country: India
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state: Maharashtra
city: Pune
country: India
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state: Maharashtra
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city: Holon
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city: Tel Hashomer
country: Israel
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city: Tel-Aviv
country: Israel
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city: Benevento
country: Italy
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city: Catania
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city: Cosenza (CS)
country: Italy
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city: Genova
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city: Milano
country: Italy
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city: Milano
country: Italy
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city: Napoli
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city: Padova
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city: Nagoya-city
country: Japan
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state: Aichi
city: Fukuoka-shi
country: Japan
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state: Fukuoka
city: Kure-city
country: Japan
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city: Sapporo-city
country: Japan
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city: Tsukuba-city
country: Japan
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state: Ibaraki
city: Morioka-city
country: Japan
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state: Iwate
city: Niigata-city
country: Japan
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state: Niigata
city: Osakasayama-city
country: Japan
facility: Research Site
state: Osaka
city: Hidaka-Shi
country: Japan
facility: Research Site
state: Saitama
city: Suntou-gun
country: Japan
facility: Research Site
state: Shizuoka
city: Chuo-ku
country: Japan
facility: Research Site
state: Tokyo
city: Yonago-city
country: Japan
facility: Research Site
state: Tottori
city: Kurume-city
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Goyang-si, Gyeonggi-do
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Daugavpils
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Johor Bahru
country: Malaysia
facility: Research Site
state: Johor
city: Kota Bahru
country: Malaysia
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state: Kelantan
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Wilayah Persekutuan
city: Mexico City
country: Mexico
facility: Research Site
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Research Site
state: Distrito Federal
city: San Luis Potosi
country: Mexico
facility: Research Site
state: San Luis PotosÃ-
city: Distrito Federal
country: Mexico
facility: Research Site
city: Lima
country: Peru
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city: Lima
country: Peru
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city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Lodz
country: Poland
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city: Lublin
country: Poland
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city: Poznan
country: Poland
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city: Warszawa
country: Poland
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city: Coimbra
country: Portugal
facility: Research Site
city: Guimaraes
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Santa Maria da Feira
country: Portugal
facility: Research Site
city: Bucharest
country: Romania
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city: Bucharest
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Targu Mures
country: Romania
facility: Research Site
city: Ivanovo
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Voronezh
country: Russian Federation
facility: Research Site
city: Ljubljana
country: Slovenia
facility: Research Site
city: Groenkloof
country: South Africa
facility: Research Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Kraaifontein
country: South Africa
facility: Research Site
state: Western Cape
city: Observatory
country: South Africa
facility: Research Site
city: Port Elizabeth
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: CÃ³rdoba
country: Spain
facility: Research Site
state: AndalucÃ-a
city: Huelva
country: Spain
facility: Research Site
state: AndalucÃ-a
city: MÃ¡laga
country: Spain
facility: Research Site
state: AndalucÃ-a
city: Sevilla
country: Spain
facility: Research Site
state: AndalucÃ-a
city: Palma de Mallorca
country: Spain
facility: Research Site
state: Baleares
city: Salamanca
country: Spain
facility: Research Site
state: Castilla LeÃ³n
city: Badalona
country: Spain
facility: Research Site
state: CataluÃ±a
city: Barcelona
country: Spain
facility: Research Site
state: CataluÃ±a
city: Barcelona
country: Spain
facility: Research Site
state: CataluÃ±a
city: Barcelona
country: Spain
facility: Research Site
state: CataluÃ±a
city: Elche
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Research Site
state: Galicia
city: Vigo
country: Spain
facility: Research Site
state: Galicia
city: San SebastiÃ¡n
country: Spain
facility: Research Site
state: PaÃ-s Vasco
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: UmeÃ¥
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Baden
country: Switzerland
facility: Research Site
city: Bellinzona
country: Switzerland
facility: Research Site
city: Chur
country: Switzerland
facility: Research Site
city: Geneva 14
country: Switzerland
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Poole
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhomme C, Richardson G, Rincon DG, Coleman RL, Herzog TJ, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Tassoudji M, Navale L, Warner DJ, Oza AM. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 Jul;15(8):799-808. doi: 10.1016/S1470-2045(14)70244-X. Epub 2014 Jun 17.
citation: Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhomme C, Richardson G, Rincon DG, Coleman RL, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Ma H, Vogl FD, Bach BA, Oza AM. Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol. 2016 Oct;143(1):27-34. doi: 10.1016/j.ygyno.2016.07.112. Epub 2016 Aug 18.
citation: Fujiwara K, Monk BJ, Lhomme C, Coleman RL, Brize A, Oaknin A, Ray-Coquard I, Fabbro M, Provencher D, Bamias A, Vergote I, DeCensi A, Zhang K, Vogl FD, Bach BA, Raspagliesi F. Health-related quality of life in women with recurrent ovarian cancer receiving paclitaxel plus trebananib or placebo (TRINOVA-1). Ann Oncol. 2016 Jun;27(6):1006-1013. doi: 10.1093/annonc/mdw147. Epub 2016 Mar 30.