Clinical trial NCT02149108: Nintedanib (BIBF 1120) vs Placebo in Refractory Metastatic Colorectal Cancer (LUME-Colon 1)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-05-29
Enrollment: 768
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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* Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity.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 oxaliplatin 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 Transferase (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.

Primary outcomes:
measure: Progression-Free Survival (PFS) by Central Review Assessment
timeFrame: From randomisation until cut-off date 14JUN2016.
measure: Overall Survival (OS)
timeFrame: From randomisation until cut-off date 14JUN2016.
Secondary outcomes:
measure: Objective Tumour Response (Complete Response (CR)) + Partial Response (PR) by Central Review Assessment
timeFrame: From randomisation until cut-off date 14JUN2016.
measure: Disease Control (Complete Response + Partial Response + Stable Disease) by Central Review Assessment
timeFrame: From randomisation until cut-off date 14JUN2016.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: 1199.52.0108 Boehringer Ingelheim Investigational Site
state: California
city: New Haven
country: United States
facility: 1199.52.0105 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Plainville
country: United States
facility: 1199.52.0101 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Arlington Heights
country: United States
facility: 1199.52.0121 Boehringer Ingelheim Investigational Site
state: Illinois
city: Sioux City
country: United States
facility: 1199.52.0123 Boehringer Ingelheim Investigational Site
state: Iowa
city: Topeka
country: United States
facility: 1199.52.0104 Boehringer Ingelheim Investigational Site
state: Kansas
city: New Orleans
country: United States
facility: 1199.52.0114 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Detroit
country: United States
facility: 1199.52.0113 Boehringer Ingelheim Investigational Site
state: Michigan
city: Omaha
country: United States
facility: 1199.52.0125 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Johnson City
country: United States
facility: 1199.52.0119 Boehringer Ingelheim Investigational Site
state: New York
city: Canton
country: United States
facility: 1199.52.0115 Boehringer Ingelheim Investigational Site
state: Ohio
city: Sylvania
country: United States
facility: 1199.52.0106 Boehringer Ingelheim Investigational Site
state: Ohio
city: Nashville
country: United States
facility: 1199.52.0102 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Fort Worth
country: United States
facility: 1199.52.0120 Boehringer Ingelheim Investigational Site
state: Texas
city: Cdad. de Córdoba
country: Argentina
facility: 1199.52.5404 Boehringer Ingelheim Investigational Site
city: Cdad. de Córdoba
country: Argentina
facility: 1199.52.5405 Boehringer Ingelheim Investigational Site
city: Ciudad Autónoma de Bs As
country: Argentina
facility: 1199.52.5401 Boehringer Ingelheim Investigational Site
city: Ciudad Autónoma de Bs As
country: Argentina
facility: 1199.52.5403 Boehringer Ingelheim Investigational Site
city: Ciudad Autónoma de Bs As
country: Argentina
facility: 1199.52.5406 Boehringer Ingelheim Investigational Site
city: Concord
country: Australia
facility: 1199.52.6102 Boehringer Ingelheim Investigational Site
state: New South Wales
city: St Leonards
country: Australia
facility: 1199.52.6103 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Wollongong
country: Australia
facility: 1199.52.6101 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Heidelberg
country: Australia
facility: 1199.52.6104 Boehringer Ingelheim Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: 1199.52.6105 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Perth
country: Australia
facility: 1199.52.6106 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Linz
country: Austria
facility: 1199.52.4302 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1199.52.4303 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1199.52.4304 Boehringer Ingelheim Investigational Site
city: Aalst
country: Belgium
facility: 1199.52.3208 Boehringer Ingelheim Investigational Site
city: Bonheiden
country: Belgium
facility: 1199.52.3205 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1199.52.3202 Boehringer Ingelheim Investigational Site
city: Charleroi
country: Belgium
facility: 1199.52.3207 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1199.52.3204 Boehringer Ingelheim Investigational Site
city: Haine-Saint-Paul
country: Belgium
facility: 1199.52.3203 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1199.52.3201 Boehringer Ingelheim Investigational Site
city: Liège
country: Belgium
facility: 1199.52.3206 Boehringer Ingelheim Investigational Site
city: Luxembourg
country: Belgium
facility: 1199.52.3521 Boehringer Ingelheim Investigational Site
city: Vancouver
country: Canada
facility: 1199.52.1003 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Edmonton
country: Canada
facility: 1199.52.1004 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1199.52.1001 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1199.52.1002 Boehringer Ingelheim Investigational Site
state: Quebec
city: Brno
country: Czechia
facility: 1199.52.4202 Boehringer Ingelheim Investigational Site
city: Hradec Kralove
country: Czechia
facility: 1199.52.4204 Boehringer Ingelheim Investigational Site
city: Prague
country: Czechia
facility: 1199.52.4201 Boehringer Ingelheim Investigational Site
city: Herning
country: Denmark
facility: 1199.52.4502 Boehringer Ingelheim Investigational Site
city: København Ø
country: Denmark
facility: 1199.52.4501 Boehringer Ingelheim Investigational Site
city: Næstved
country: Denmark
facility: 1199.52.4503 Boehringer Ingelheim Investigational Site
city: Odense C
country: Denmark
facility: 1199.52.4504 Boehringer Ingelheim Investigational Site
city: Lille cedex
country: France
facility: 1199.52.3304 Boehringer Ingelheim Investigational Site
city: Lyon cedex 8
country: France
facility: 1199.52.3307 Boehringer Ingelheim Investigational Site
city: Paris cedex 15
country: France
facility: 1199.52.3305 Boehringer Ingelheim Investigational Site
city: Reims Cedex
country: France
facility: 1199.52.3301 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 1199.52.4906 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1199.52.4905 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1199.52.4904 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1199.52.4903 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 1199.52.4901 Boehringer Ingelheim Investigational Site
city: Hong Kong
country: Hong Kong
facility: 1199.52.8501 Boehringer Ingelheim Investigational Site
city: Hong Kong
country: Hong Kong
facility: 1199.52.8502 Boehringer Ingelheim Investigational Site
city: Hong Kong
country: Hong Kong
facility: 1199.52.8503 Boehringer Ingelheim Investigational Site
city: Hong Kong
country: Hong Kong
facility: 1199.52.8504 Boehringer Ingelheim Investigational Site
city: Beer Sheva
country: Israel
facility: 1199.52.9706 Boehringer Ingelheim Investigational Site
city: Petach Tikva
country: Israel
facility: 1199.52.9704 Boehringer Ingelheim Investigational Site
city: Tel Aviv
country: Israel
facility: 1199.52.9703 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1199.52.3901 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1199.52.3906 Boehringer Ingelheim Investigational Site
city: Napoli
country: Italy
facility: 1199.52.3907 Boehringer Ingelheim Investigational Site
city: Padova
country: Italy
facility: 1199.52.3905 Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 1199.52.3903 Boehringer Ingelheim Investigational Site
city: San Giovanni Rotondo (FG)
country: Italy
facility: 1199.52.3904 Boehringer Ingelheim Investigational Site
city: Aichi, Nagoya
country: Japan
facility: 1199.52.8102 Boehringer Ingelheim Investigational Site
city: Chiba, Chiba
country: Japan
facility: 1199.52.8105 Boehringer Ingelheim Investigational Site
city: Chiba, Kashiwa
country: Japan
facility: 1199.52.8101 Boehringer Ingelheim Investigational Site
city: Ehime, Matsuyama
country: Japan
facility: 1199.52.8107 Boehringer Ingelheim Investigational Site
city: Fukuoka, Fukuoka
country: Japan
facility: 1199.52.8106 Boehringer Ingelheim Investigational Site
city: Hokkaido, Sapporo
country: Japan
facility: 1199.52.8108 Boehringer Ingelheim Investigational Site
city: Hyogo, Amagasaki
country: Japan
facility: 1199.52.8115 Boehringer Ingelheim Investigational Site
city: Hyogo, Kobe
country: Japan
facility: 1199.52.8112 Boehringer Ingelheim Investigational Site
city: Ibaraki, Tsukuba
country: Japan
facility: 1199.52.8114 Boehringer Ingelheim Investigational Site
city: Oita, Yufu
country: Japan
facility: 1199.52.8110 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1199.52.8116 Boehringer Ingelheim Investigational Site
city: Osaka, Suita
country: Japan
facility: 1199.52.8103 Boehringer Ingelheim Investigational Site
city: Saitama, Kitaadachi-gun
country: Japan
facility: 1199.52.8109 Boehringer Ingelheim Investigational Site
city: Shizuoka, Sunto-gun
country: Japan
facility: 1199.52.8104 Boehringer Ingelheim Investigational Site
city: Tokyo , Shinagawa-ku
country: Japan
facility: 1199.52.8113 Boehringer Ingelheim Investigational Site
city: Tokyo, Koto-ku
country: Japan
facility: 1199.52.8111 Boehringer Ingelheim Investigational Site
city: Goyang
country: Korea, Republic of
facility: 1199.52.8202 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.52.8201 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.52.8203 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1199.52.8204 Boehringer Ingelheim Investigational Site
city: Mexico
country: Mexico
facility: 1199.52.5201 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1199.52.3101 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1199.52.3103 Boehringer Ingelheim Investigational Site
city: Utrecht
country: Netherlands
facility: 1199.52.3102 Boehringer Ingelheim Investigational Site
city: Jelenia Gora
country: Poland
facility: 1199.52.4801 Boehringer Ingelheim Investigational Site
city: Poznan
country: Poland
facility: 1199.52.4803 Boehringer Ingelheim Investigational Site
city: Wroclaw
country: Poland
facility: 1199.52.4804 Boehringer Ingelheim Investigational Site
city: Almada
country: Portugal
facility: 1199.52.3504 Boehringer Ingelheim Investigational Site
city: Coimbra
country: Portugal
facility: 1199.52.3502 Boehringer Ingelheim Investigational Site
city: Loures
country: Portugal
facility: 1199.52.3505 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1199.52.3501 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1199.52.3506 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1199.52.0701 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1199.52.0703 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1199.52.0702 Boehringer Ingelheim Investigational Site
city: Tyumen
country: Russian Federation
facility: 1199.52.0707 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1199.52.3401 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: 1199.52.3402 Boehringer Ingelheim Investigational Site
city: La Coruña
country: Spain
facility: 1199.52.3406 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1199.52.3403 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1199.52.3404 Boehringer Ingelheim Investigational Site
city: Santander
country: Spain
facility: 1199.52.3405 Boehringer Ingelheim Investigational Site
city: Sevilla
country: Spain
facility: 1199.52.3407 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 1199.52.4601 Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: 1199.52.4602 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1199.52.8805 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1199.52.8801 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1199.52.8803 Boehringer Ingelheim Investigational Site
city: Taoyuan County
country: Taiwan
facility: 1199.52.8802 Boehringer Ingelheim Investigational Site
city: Adana
country: Turkey
facility: 1199.52.9005 Boehringer Ingelheim Investigational Site
city: Ankara
country: Turkey
facility: 1199.52.9001 Boehringer Ingelheim Investigational Site
city: Antalya
country: Turkey
facility: 1199.52.9003 Boehringer Ingelheim Investigational Site
city: Istanbul
country: Turkey
facility: 1199.52.9004 Boehringer Ingelheim Investigational Site
city: Izmir
country: Turkey
facility: 1199.52.9002 Boehringer Ingelheim Investigational Site
city: Aberdeen
country: United Kingdom
facility: 1199.52.4401 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 1199.52.4403 Boehringer Ingelheim Investigational Site
city: Middlesex
country: United Kingdom
facility: 1199.52.4402 Boehringer Ingelheim Investigational Site
city: Nottingham
country: United Kingdom
facility: 1199.52.4405 Boehringer Ingelheim Investigational Site
city: Southampton
country: United Kingdom
facility: 1199.52.4404 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Van Cutsem E, Yoshino T, Lenz HJ, Lonardi S, Falcone A, Limon ML, Saunders M, Sobrero A, Park YS, Ferreiro R, Hong YS, Tomasek J, Taniguchi H, Ciardiello F, Stoehr J, Oum'Hamed Z, Vlassak S, Studeny M, Argiles G. Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): a phase III, international, randomized, placebo-controlled study. Ann Oncol. 2018 Sep 1;29(9):1955-1963. doi: 10.1093/annonc/mdy241.
citation: Van Cutsem E, Yoshino T, Hocke J, Oum'Hamed Z, Studeny M, Tabernero J. Rationale and Design for the LUME-Colon 1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Nintedanib Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Patients With Advanced Colorectal Cancer Refractory to Standard Treatment. Clin Colorectal Cancer. 2016 Mar;15(1):91-94.e1. doi: 10.1016/j.clcc.2015.09.005. Epub 2015 Oct 9.