Nintedanib (BIBF 1120) vs Placebo in Refractory Metastatic Colorectal Cancer (LUME-Colon 1)

Colorectal Neoplasms Clinical Trial

Official title:

A Double-blind, Randomised, Placebo Controlled Phase III Study of Nintedanib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Metastatic Colorectal Cancer Refractory to Standard Therapies.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02149108
• Other study ID #: 1199.52
• Secondary ID: 2012-000095-42
• Status: Completed
• Phase: Phase 3
• First received: May 26, 2014
• Last updated: August 26, 2016
• Start date: September 2014
• Est. completion date: August 2016

Study information

• Verified date: August 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Dept of Health and Ageing Therapeutic Goods AdministrationAustria: Austrian Medicines and Medical Devices AgencyBelgium: Federal Agency for Medicinal and Health ProductsCanada: Health CanadaCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFrance: Agence Nationale sécurité médicament et des produits santéGermany: Federal Institute for Drugs and Medical DevicesHong Kong: Department of HealthIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: AIFA (Italian Medicine Agency)Japan: Ministry of Health, Labor and WelfareKorea: Ministry of Food and Drug SafetyLuxembourg: Ministère de la SantéMexico: Federal Commission for Protection Against Health RisksNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Registration Medicinal Product Medical Device Biocidal ProductRussia: Pharmacological Committee, Ministry of HealthSpain: Spanish Agency of Medicines and Medical DevicesSweden: Medical Products AgencyTaiwan : Food and Drug AdministrationTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug AdministrationPortugal: INFARMED, National Authority of Medicines and Health Products, IP
• Study type: Interventional

Clinical Trial Summary

The objective of this Phase III study is to evaluate the efficacy of nintedanib in patients with metastatic colorectal cancer (mCRC) after failure of previous treatment with standard chemotherapy and biological agents.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 768
• Est. completion date: August 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Age >= 18 years

• Signed informed consent

• Histologically or cytologically confirmed colorectal adenocarcinoma

• Metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy

• Eastern Cooperative Oncology Group (ECOG) performance status = 1

• At least one measurable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1

• Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following:

• - fluoropyrimidine

• - oxaliplatin: Patients treated with oxalipatin in adjuvant setting should have progressed within 6 months of completion of adjuvant therapy or they must have been treated with oxaliplatin for metastatic disease

• - irinotecan

• - bevacizumab or aflibercept

• - cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumours

• - The remaining standard available therapy as recommended by investigator is best supportive care (note: previous treatment with regorafenib and TAS 102 are allowed and these agents should be administered before study if available to patient according to local standards)

• - Life expectancy of at least 12 weeks

• - Hepatic function: aspartate aminotransferase (AST)/ Alanine Amino Tranferase (ALT) = 1.5 X Upper Limit of Normal (ULN) and bilirubin = ULN for patients without liver metastases. AST/ALT = 2.5 X ULN and bilirubin = ULN for patients with liver metastases. Patients with Gilbert syndrome and bilirubin < 2 X ULN and normal AST/ALT are eligible

• Coagulation parameters: International normalised ratio (INR) < 2 and partial prothrombin Time (PTT) = 2xULN

Exclusion criteria:

• Previous treatment with nintedanib

• toxicity attributed to previous anticancer therapy that did not resolve to Common Terminology Criteria for Adverse Events (CTCAE) grade =1

• History of other malignancies in the last 5 years, in particular those that could interfere with interpretation of results.

• Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,

• Significant cardiovascular diseases

• History of severe haemorrhagic or thromboembolic event in the past 12 months

• Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeutic INR monitoring

• Gastrointestinal disorders or abnormalities that would interfere with absorption of study drug

• Patient with brain metastases that are symptomatic and/or require therapy.

• Patients of childbearing potential who are sexually active and unwilling to use a highly effective method of contraception

• Pregnancy or breast-feeding.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• Nindetanib (BIBF 1120)

• Placebo

• BSC

• BSC

Locations

Country	Name	City	State
Argentina	1199.52.5404 Boehringer Ingelheim Investigational Site	Cdad. de Córdoba
Argentina	1199.52.5405 Boehringer Ingelheim Investigational Site	Cdad. de Córdoba
Argentina	1199.52.5401 Boehringer Ingelheim Investigational Site	Ciudad Autónoma de Bs As
Argentina	1199.52.5403 Boehringer Ingelheim Investigational Site	Ciudad Autónoma de Bs As
Argentina	1199.52.5406 Boehringer Ingelheim Investigational Site	Ciudad Autónoma de Bs As
Australia	1199.52.6102 Boehringer Ingelheim Investigational Site	Concord	New South Wales
Australia	1199.52.6104 Boehringer Ingelheim Investigational Site	Heidelberg	Victoria
Australia	1199.52.6105 Boehringer Ingelheim Investigational Site	Nedlands	Western Australia
Australia	1199.52.6106 Boehringer Ingelheim Investigational Site	Perth	Western Australia
Australia	1199.52.6103 Boehringer Ingelheim Investigational Site	St Leonards	New South Wales
Australia	1199.52.6101 Boehringer Ingelheim Investigational Site	Wollongong	New South Wales
Austria	1199.52.4302 Boehringer Ingelheim Investigational Site	Linz
Austria	1199.52.4303 Boehringer Ingelheim Investigational Site	Wien
Austria	1199.52.4304 Boehringer Ingelheim Investigational Site	Wien
Belgium	1199.52.3208 Boehringer Ingelheim Investigational Site	Aalst
Belgium	1199.52.3205 Boehringer Ingelheim Investigational Site	Bonheiden
Belgium	1199.52.3202 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1199.52.3207 Boehringer Ingelheim Investigational Site	Charleroi
Belgium	1199.52.3204 Boehringer Ingelheim Investigational Site	Edegem
Belgium	1199.52.3203 Boehringer Ingelheim Investigational Site	Haine-Saint-Paul
Belgium	1199.52.3201 Boehringer Ingelheim Investigational Site	Leuven
Belgium	1199.52.3206 Boehringer Ingelheim Investigational Site	Liège
Belgium	1199.52.3521 Boehringer Ingelheim Investigational Site	Luxembourg
Canada	1199.52.1004 Boehringer Ingelheim Investigational Site	Edmonton	Ontario
Canada	1199.52.1002 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1199.52.1001 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1199.52.1003 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Czech Republic	1199.52.4202 Boehringer Ingelheim Investigational Site	Brno
Czech Republic	1199.52.4204 Boehringer Ingelheim Investigational Site	Hradec Kralove
Czech Republic	1199.52.4201 Boehringer Ingelheim Investigational Site	Prague
Denmark	1199.52.4502 Boehringer Ingelheim Investigational Site	Herning
Denmark	1199.52.4501 Boehringer Ingelheim Investigational Site	København Ø
Denmark	1199.52.4503 Boehringer Ingelheim Investigational Site	Næstved
Denmark	1199.52.4504 Boehringer Ingelheim Investigational Site	Odense C
France	1199.52.3304 Boehringer Ingelheim Investigational Site	Lille cedex
France	1199.52.3307 Boehringer Ingelheim Investigational Site	Lyon cedex 8
France	1199.52.3305 Boehringer Ingelheim Investigational Site	Paris cedex 15
France	1199.52.3301 Boehringer Ingelheim Investigational Site	Reims Cedex
Germany	1199.52.4906 Boehringer Ingelheim Investigational Site	Dresden
Germany	1199.52.4905 Boehringer Ingelheim Investigational Site	Essen
Germany	1199.52.4904 Boehringer Ingelheim Investigational Site	Freiburg
Germany	1199.52.4903 Boehringer Ingelheim Investigational Site	Mannheim
Germany	1199.52.4901 Boehringer Ingelheim Investigational Site	Ulm
Hong Kong	1199.52.8501 Boehringer Ingelheim Investigational Site	Hong Kong
Hong Kong	1199.52.8502 Boehringer Ingelheim Investigational Site	Hong Kong
Hong Kong	1199.52.8503 Boehringer Ingelheim Investigational Site	Hong Kong
Hong Kong	1199.52.8504 Boehringer Ingelheim Investigational Site	Hong Kong
Israel	1199.52.9706 Boehringer Ingelheim Investigational Site	Beer Sheva
Israel	1199.52.9704 Boehringer Ingelheim Investigational Site	Petach Tikva
Israel	1199.52.9703 Boehringer Ingelheim Investigational Site	Tel Aviv
Italy	1199.52.3901 Boehringer Ingelheim Investigational Site	Genova
Italy	1199.52.3906 Boehringer Ingelheim Investigational Site	Milano
Italy	1199.52.3907 Boehringer Ingelheim Investigational Site	Napoli
Italy	1199.52.3905 Boehringer Ingelheim Investigational Site	Padova
Italy	1199.52.3903 Boehringer Ingelheim Investigational Site	Pisa
Italy	1199.52.3904 Boehringer Ingelheim Investigational Site	San Giovanni Rotondo (FG)
Japan	1199.52.8102 Boehringer Ingelheim Investigational Site	Aichi, Nagoya
Japan	1199.52.8105 Boehringer Ingelheim Investigational Site	Chiba, Chiba
Japan	1199.52.8101 Boehringer Ingelheim Investigational Site	Chiba, Kashiwa
Japan	1199.52.8107 Boehringer Ingelheim Investigational Site	Ehime, Matsuyama
Japan	1199.52.8106 Boehringer Ingelheim Investigational Site	Fukuoka, Fukuoka
Japan	1199.52.8108 Boehringer Ingelheim Investigational Site	Hokkaido, Sapporo
Japan	1199.52.8115 Boehringer Ingelheim Investigational Site	Hyogo, Amagasaki
Japan	1199.52.8112 Boehringer Ingelheim Investigational Site	Hyogo, Kobe
Japan	1199.52.8114 Boehringer Ingelheim Investigational Site	Ibaraki, Tsukuba
Japan	1199.52.8110 Boehringer Ingelheim Investigational Site	Oita, Yufu
Japan	1199.52.8116 Boehringer Ingelheim Investigational Site	Osaka, Osaka
Japan	1199.52.8103 Boehringer Ingelheim Investigational Site	Osaka, Suita
Japan	1199.52.8109 Boehringer Ingelheim Investigational Site	Saitama, Kitaadachi-gun
Japan	1199.52.8104 Boehringer Ingelheim Investigational Site	Shizuoka, Sunto-gun
Japan	1199.52.8113 Boehringer Ingelheim Investigational Site	Tokyo , Shinagawa-ku
Japan	1199.52.8111 Boehringer Ingelheim Investigational Site	Tokyo, Koto-ku
Korea, Republic of	1199.52.8202 Boehringer Ingelheim Investigational Site	Goyang
Korea, Republic of	1199.52.8201 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.52.8203 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.52.8204 Boehringer Ingelheim Investigational Site	Seoul
Mexico	1199.52.5201 Boehringer Ingelheim Investigational Site	Mexico
Netherlands	1199.52.3101 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1199.52.3103 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1199.52.3102 Boehringer Ingelheim Investigational Site	Utrecht
Poland	1199.52.4801 Boehringer Ingelheim Investigational Site	Jelenia Gora
Poland	1199.52.4803 Boehringer Ingelheim Investigational Site	Poznan
Poland	1199.52.4804 Boehringer Ingelheim Investigational Site	Wroclaw
Portugal	1199.52.3504 Boehringer Ingelheim Investigational Site	Almada
Portugal	1199.52.3502 Boehringer Ingelheim Investigational Site	Coimbra
Portugal	1199.52.3505 Boehringer Ingelheim Investigational Site	Loures
Portugal	1199.52.3501 Boehringer Ingelheim Investigational Site	Porto
Portugal	1199.52.3506 Boehringer Ingelheim Investigational Site	Porto
Russian Federation	1199.52.0701 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1199.52.0703 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1199.52.0702 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1199.52.0707 Boehringer Ingelheim Investigational Site	Tyumen
Spain	1199.52.3401 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1199.52.3402 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat
Spain	1199.52.3406 Boehringer Ingelheim Investigational Site	La Coruña
Spain	1199.52.3403 Boehringer Ingelheim Investigational Site	Madrid
Spain	1199.52.3404 Boehringer Ingelheim Investigational Site	Madrid
Spain	1199.52.3405 Boehringer Ingelheim Investigational Site	Santander
Spain	1199.52.3407 Boehringer Ingelheim Investigational Site	Sevilla
Sweden	1199.52.4601 Boehringer Ingelheim Investigational Site	Stockholm
Sweden	1199.52.4602 Boehringer Ingelheim Investigational Site	Uppsala
Taiwan	1199.52.8805 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1199.52.8801 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1199.52.8803 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1199.52.8802 Boehringer Ingelheim Investigational Site	Taoyuan County
Turkey	1199.52.9005 Boehringer Ingelheim Investigational Site	Adana
Turkey	1199.52.9001 Boehringer Ingelheim Investigational Site	Ankara
Turkey	1199.52.9003 Boehringer Ingelheim Investigational Site	Antalya
Turkey	1199.52.9004 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	1199.52.9002 Boehringer Ingelheim Investigational Site	Izmir
United Kingdom	1199.52.4401 Boehringer Ingelheim Investigational Site	Aberdeen
United Kingdom	1199.52.4403 Boehringer Ingelheim Investigational Site	Manchester
United Kingdom	1199.52.4402 Boehringer Ingelheim Investigational Site	Middlesex
United Kingdom	1199.52.4405 Boehringer Ingelheim Investigational Site	Nottingham
United Kingdom	1199.52.4404 Boehringer Ingelheim Investigational Site	Southampton
United States	1199.52.0121 Boehringer Ingelheim Investigational Site	Arlington Heights	Illinois
United States	1199.52.0115 Boehringer Ingelheim Investigational Site	Canton	Ohio
United States	1199.52.0113 Boehringer Ingelheim Investigational Site	Detroit	Michigan
United States	1199.52.0120 Boehringer Ingelheim Investigational Site	Fort Worth	Texas
United States	1199.52.0119 Boehringer Ingelheim Investigational Site	Johnson City	New York
United States	1199.52.0108 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	1199.52.0102 Boehringer Ingelheim Investigational Site	Nashville	Tennessee
United States	1199.52.0105 Boehringer Ingelheim Investigational Site	New Haven	Connecticut
United States	1199.52.0114 Boehringer Ingelheim Investigational Site	New Orleans	Louisiana
United States	1199.52.0125 Boehringer Ingelheim Investigational Site	Omaha	Nebraska
United States	1199.52.0101 Boehringer Ingelheim Investigational Site	Plainville	Connecticut
United States	1199.52.0123 Boehringer Ingelheim Investigational Site	Sioux City	Iowa
United States	1199.52.0106 Boehringer Ingelheim Investigational Site	Sylvania	Ohio
United States	1199.52.0104 Boehringer Ingelheim Investigational Site	Topeka	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Czech Republic,  Denmark,  France,  Germany,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) by Central Review Assessment		22 months	No
Primary	Overall Survival (OS) by Central Review Assessment		22 months	No
Secondary	Objective Tumour Response (Complete Response + Partial Response) by Central Review Assessment		22 months	No
Secondary	Disease control (Complete Response + Partial Response + Stable Disease) by Central Review Assessment		22 months	No