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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01204749
• Other study ID #: 20090508
• Status: Completed
• Phase: Phase 3
• First received: August 26, 2010
• Last updated: December 14, 2016
• Start date: November 2010
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Evaluation CenterMalaysia: National Pharmaceutical Control BureauMexico: Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)Mexico: SSA (Secretaria de Salud Publica)Peru: INS (Instituto Nacional de Salud)Portugal: Instituto Nacional da Farmácia e do Medicamento (INFARMED)Romania: National Medicines AgencySlovenia: Agency for Medicinal Products and Medicinal Devices of the Republic of Slovenia (ARSZMP)South Korea: Korea Food and Drug AdministrationSpain: Agencia Española de Medicamentos y Productos SanitariosSwitzerland: Swissmedic (Swiss Agency for Therapeutic Products)United States: Food and Drug AdministrationAustralia: Therapeutic Goods AdministrationBrazil: ANVISA (Agência Nacional de Vigilância Sanitária)Bulgaria: Bulgarian Drug AgencyCanada: Health CanadaChile: Instituto De Salud Pública de Chile (ISP)Japan: Ministry of Health, Labor and WelfareCroatia: Ministarstvo zdravstva i socijalne skrbi (Ministry of Health and Social Welfare)Czech Republic: Statni ustav pro kontrolu lecivUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyHong Kong: Department of HealthLatvia: State Agency of MedicinesFrance: Agence nationale de sécurité du médicament et des produits de santé (ANSM)India: Central Drugs Standard Control OrganizationBelgium: Federal Agency for Medicinal Products and Health ProductsGreece: National Organization of MedicinesItaly: Agenzia Italiana del Farmaco (AIFA)Poland: Office for Registration of Medicinal ProductsSouth Africa: Medicines Control CouncilSweden: Medical Products AgencyRussia: The Ministry of Healthcare of the Russian FederationIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 919
• Est. completion date: December 2016
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Primary Peritoneal Cancer

Intervention

Drug:
• AMG 386
Weekly Intravenous (IV) AMG 386 15 mg/kg
• AMG 386 Placebo
Weekly Intravenous (IV) placebo 15 mg/kg
• Paclitaxel
Paclitaxel 80 mg/m2 intravenous (IV) weekly (3 on/1 off)
• Paclitaxel
Paclitaxel 80 mg/m2 intravenous (IV) weekly (3 on/1 off)

Locations

Country	Name	City	State
Australia	Research Site	Bendigo	Victoria
Australia	Research Site	Bentleigh East	Victoria
Australia	Research Site	Footscray	Victoria
Australia	Research Site	Greenslopes	Queensland
Australia	Research Site	Malvern	Victoria
Australia	Research Site	New Lambton Heights	New South Wales
Australia	Research Site	Parkville	Victoria
Belgium	Research Site	Edegem
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
Brazil	Research Site	ItajaÃ-	Santa Catarina
Brazil	Research Site	Porto Alegre	Rio Grande do Sul
Brazil	Research Site	Porto Alegre	Rio Grande do Sul
Brazil	Research Site	Ribeirao Preto	São Paulo
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Gabrovo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Canada	Research Site	Calgary	Alberta
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Chile	Research Site	Temuco	CautÃ-n
Chile	Research Site	Valparaiso	ValparaÃ-so
Croatia	Research Site	Zagreb
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Praha 2
Czech Republic	Research Site	Praha 5
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
France	Research Site	Amiens
France	Research Site	Angers
France	Research Site	Avignon Cedex 2
France	Research Site	Bayonne
France	Research Site	Besancon Cedex
France	Research Site	Bordeaux Cedex
France	Research Site	Bordeaux Cedex
France	Research Site	Brest Cedex 2
France	Research Site	Dijon
France	Research Site	Le Mans
France	Research Site	Lille Cedex
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Marseille cedex 05
France	Research Site	Marseille Cedex 09
France	Research Site	Montpellier Cedex 5
France	Research Site	Nancy
France	Research Site	Nantes Cedex 2
France	Research Site	Nice cedex 2
France	Research Site	Orléans cedex 2
France	Research Site	Périgueux cedex
France	Research Site	Paris cedex 15
France	Research Site	Reims Cedex
France	Research Site	Saint Grégoire cedex
France	Research Site	Saint Herblain
France	Research Site	Strasbourg
France	Research Site	Villejuif cedex
Greece	Research Site	Athens
Greece	Research Site	Heraklion
Greece	Research Site	Larissa
Greece	Research Site	Patra
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	Hong Kong
India	Research Site	Hyderabad	Andhra Pradesh
India	Research Site	Mumbai	Maharashtra
India	Research Site	Nashik	Maharashtra
India	Research Site	Pune	Maharashtra
India	Research Site	Pune	Maharashtra
Israel	Research Site	Haifa
Israel	Research Site	Holon
Israel	Research Site	Kefar Sava
Israel	Research Site	Tel Hashomer
Israel	Research Site	Tel-Aviv
Italy	Research Site	Benevento
Italy	Research Site	Catania
Italy	Research Site	Cosenza (CS)
Italy	Research Site	Genova
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Potenza
Italy	Research Site	Roma
Italy	Research Site	Roma
Japan	Research Site	Chuo-ku	Tokyo
Japan	Research Site	Fukuoka-shi	Fukuoka
Japan	Research Site	Hidaka-Shi	Saitama
Japan	Research Site	Kure-city	Hiroshima
Japan	Research Site	Kurume-city
Japan	Research Site	Morioka-city	Iwate
Japan	Research Site	Nagoya-city	Aichi
Japan	Research Site	Niigata-city	Niigata
Japan	Research Site	Osakasayama-city	Osaka
Japan	Research Site	Sapporo-city	Hokkaido
Japan	Research Site	Suntou-gun	Shizuoka
Japan	Research Site	Tokyo
Japan	Research Site	Tokyo
Japan	Research Site	Tokyo
Japan	Research Site	Tsukuba-city	Ibaraki
Japan	Research Site	Yonago-city	Tottori
Korea, Republic of	Research Site	Goyang-si, Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Latvia	Research Site	Daugavpils
Latvia	Research Site	Riga
Latvia	Research Site	Riga
Malaysia	Research Site	Johor Bahru	Johor
Malaysia	Research Site	Kota Bahru	Kelantan
Malaysia	Research Site	Kuala Lumpur	Wilayah Persekutuan
Mexico	Research Site	Distrito Federal
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	San Luis Potosi	San Luis PotosÃ-
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Portugal	Research Site	Coimbra
Portugal	Research Site	Guimaraes
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Portugal	Research Site	Santa Maria da Feira
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Cluj Napoca
Romania	Research Site	Suceava
Romania	Research Site	Targu Mures
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Voronezh
Slovenia	Research Site	Ljubljana
South Africa	Research Site	Groenkloof	Gauteng
South Africa	Research Site	Johannesburg	Gauteng
South Africa	Research Site	Kraaifontein	Western Cape
South Africa	Research Site	Observatory
South Africa	Research Site	Port Elizabeth
South Africa	Research Site	Pretoria
Spain	Research Site	Badalona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Córdoba	AndalucÃ-a
Spain	Research Site	Elche	Comunidad Valenciana
Spain	Research Site	Huelva	AndalucÃ-a
Spain	Research Site	Málaga	AndalucÃ-a
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Palma de Mallorca	Baleares
Spain	Research Site	Salamanca	Castilla León
Spain	Research Site	San Sebastián	PaÃ-s Vasco
Spain	Research Site	Santiago de Compostela	Galicia
Spain	Research Site	Sevilla	AndalucÃ-a
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Vigo	Galicia
Sweden	Research Site	Umeå
Sweden	Research Site	Uppsala
Switzerland	Research Site	Baden
Switzerland	Research Site	Bellinzona
Switzerland	Research Site	Chur
Switzerland	Research Site	Geneva 14
Switzerland	Research Site	Zurich
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Poole
United Kingdom	Research Site	Sutton
United States	Research Site	Abington	Pennsylvania
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boise	Idaho
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Brightwaters	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Danbury	Connecticut
United States	Research Site	Englewood	Colorado
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Hollywood	Florida
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Houston	Texas
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Los Angeles	California
United States	Research Site	Metairie	Louisiana
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Ogden	Utah
United States	Research Site	Orlando	Florida
United States	Research Site	Peoria	Illinois
United States	Research Site	Phoenix	Arizona
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Skokie	Illinois
United States	Research Site	Stanford	California
United States	Research Site	Tacoma	Washington
United States	Research Site	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Croatia,  Czech Republic,  Estonia,  France,  Greece,  Hong Kong,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Malaysia,  Mexico,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Slovenia,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (2)

Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón 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. — View Citation

Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival		8 Months on average	No
Secondary	Overall survival		20 months on average	No
Secondary	Objective Response Rate		From Baseline (if subject has Measurable Disease) until objective response (radiologic)	No
Secondary	Duration of response		From Baseline until progression	No
Secondary	CA-125 response rate per Gynecologic Cancer Intergroup (GCIG) and change in CA-125		From Baseline until CA-125 response	No
Secondary	Incidence of adverse events and significant laboratory abnormalities		8 Months on average	Yes
Secondary	Pharmacokinetics of AMG 386 (Cmax and Cmin)		Week 1 until week 9 of treatment	No
Secondary	Incidence of the occurrence of anti-AMG 386 antibody formation		Week 1 until maximum of 1-year following last dose of study drug	Yes
Secondary	Patient reported Health Related Quality of Life (HRQOL) and ovarian cancer related symptoms using Functional Assessment of Cancer Therapy - Ovary questionnaire (FACT-O)		From week 1 until 30-days following last study drug administration	No
Secondary	Overall health status using EuroQOL(EQ-5D)		From week 1 until 30-days following last study drug administration	No

External Links

•   AmgenTrials clinical trials website