Alternative Drug Names:
Nintedanib was called BIBF 1120 (Ofev brand in the US)
Purpose of Trial:
The purpose of this phase 2 study is to evaluate the safety and efficacy of Nintedanib in the setting of metastatic IBC. Nintedanib is FDA approved outside of oncology, for idiopathic pulmonary fibrosis, which is a lung disease. The mechanism how this drug works is via inhibiting the formation of blood vessels (the process is called angiogenesis). Tumors actively release signals that give rise to new blood vessels, and this helps to bring oxygen and nutrients to the growing tumor. Therefore, the concept behind this drug is that inhibiting blood vessel formation will starve the tumor and slow its growth.
Why this study is relevant for IBC patients:
Angiogenesis is known to be a process that IBC cells highly up-regulate to survive. This may be because of the fast proliferation rate, as well as the webby nature of IBC meaning that many blood vessels are formed in different orientations.
Nintedanib is a multi-tyrosine kinase inhibitor. It is a potent small molecule inhibitor of the receptor tyrosine kinases PDGFR, FGFR and VEGFR (all involved in angiogenesis) as well as Src and FLT-3. Here is a review paper on this drug. Here is a paper (full text) regarding a clinical trial in breast cancer performed in Spain, dosed in combination with paclitaxel, with information about the toxicities and efficacy. Here is another paper (full text) regarding the patient-reported outcomes in a lung cancer clinical trial – overall quite good tolerability even with chemotherapy.
This trial is for HER2 negative (ie TNBC or ER+) metastatic IBC patients who have had 2 or more chemotherapies in the metastatic/recurrent setting, and have progressed on their most recent therapy. Biopsy tissue must be available for biomarker studies, but it does not have to be new. There is a long list of exclusion criteria that are specific to this trial because of safety issues known with angiogenesis inhibitors. See the clinicaltrials.gov link below for information.
Nintedanib is an oral tablet you will take twice daily (about 12 hours apart) every day for 28 days in each cycle. Everyone will receive the drug (i.e. no placebo).
To participate in this trial, you will need to travel every 4 weeks to MD Anderson for the first 7 months, and then every 2 months after that if you have a local oncologist willing to follow up with you. Each cycle lasts 28 days, and you will take the drug continuously every day throughout the cycle. At each visit you will have a physical exam, and blood draws prior to receiving the drugs – then you will be able to go home. Scans to monitor response will be every 2 cycles if the doctor thinks it is needed, and if the results show that the drug is working, you will continue to receive it. Additional studies such as heart monitoring may be added if the doctor thinks it is needed. You can stop at any time if the side effects are too intolerable. If you are responding and tolerating it well, you may continue this treatment for up to 24 months. After stopping the drug, you will receive follow up phone calls from the research team every 3 months for a year that should last about 2 minutes each to document any lasting problems.
Location of Trial:
Only at MD Anderson Cancer Center in Houston, TX (NCI comprehensive cancer center)
For more information:
Contact the principal investigator, Dr Naoto Ueno at 713-792-2817
Is this study NCI Compliant?:
NCT trial number & link:
NCT# 02389764 – click for more info
Poster from scientific meeting: