A double-blind, randomized, placebo controlled Phase III study of Nintedanib plus best supportive care (BSC) versus placebo plus BSC in patients with colorectal cancer refractory to standard therapies.

Study Objective:

The objective is to compare the efficacy and safety of Nintedanib plus best standard of care with placebo plus best standard of care.

Participation conditions

Inclusion criteria:

Patients must

1. Be 18 yo and older
2. Have signed informed consent
3. Have colorectal adenocarcinoma confirmed histologically or cytologically
4. Have metastatic or locally advanced disease not amenable to curative surgery and/or radiotherapy
5. Have an ECOG performance status ≤ 1
6. Have at least one measurable lesion according to RECIST 1.1
7. Be in progression on standard therapies or have withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following: flouropyrimidine, oxaliplatin, irinotecan, bevacizumab or aflibercept, cetuximab or panitumumab for patients with K-Ras wt or Ras wt tumours
8. Have best supportive care as the remaining standard available therapy per investigator recommendations
9. Have a minimal time interval of 3 weeks between the last administration of CRC treatment (cytotoxics or targeted agents) and randomisation
10. Have a life expectancy of at least 12 weeks
11. Have a serum creatinine ≤ 1.5 x ULN
12. Have a proteinuria ≤ grade 2 by CTCAE
13. Have specific biological parameters within the normal range (per protocol)

Exclusion criteria

Patients must NOT

1. Have received previous treatment with Nintedanib.
2. Have known hypersensitivity to the trial drugs or their excipients.
3. Have experienced toxicity attributed to previous anticancer therapy that did not resolve to CTCAE grade ≤1 with exception of Hb, alopecia, pigmentation and oxaliplatin related neurotoxicity.
4. Have history of other malignancies in the last 5 years (exceptions per protocol).
5. Have serious concomitant diseases or medical conditions affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug.
6. Have major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period.
7. Have significant cardiovascular diseases.
8. Have history of severe haemorrhagic or thromboembolic event in the past 12 months (exception per protocol). Must not have known inherited predisposition to bleeding or to thrombosis.
9. Have bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeutic INR monitoring.
10. Have Inflammatory bowel disease and other serious medical conditions increasing the risk of perforation or bleeding according to investigator’s judgment.
11. Have gastrointestinal disorders or abnormalities that would interfere with absorption of study drug.
12. Have brain metastases that are symptomatic and/or require therapy.
13. Have Active alcohol or drug abuse behaviours.
14. Be unwilling to use a highly effective method of contraception during the trial and for at least 3 months after the end of the treatment with Nintedanib if they are sexually active patients of childbearing potential.
15. Have ongoing pregnancy or breast-feeding.
16. Be unable to comply with the protocol

Participating centers:

Centre Hospitalier de Luxembourg (CHL)  

Centre Hospitalier Emile Mayrisch (CHEM)