Efficacy and Safety of High Dose Aprepitant Treatment in Patients With Advanced Non-Small Cell Lung Cancer
Status:
Recruiting
Trial end date:
2021-12-15
Target enrollment:
Participant gender:
Summary
Lung cancer is one of the most common causes of cancer death in worldwide. It is projected
that the vast majority, approximately 80% -85% of all lung cancer diagnosis is Non-Small Cell
Lung Cancer (NSCLC). Although there are significant improvements in the treatment of Lung
Cancer in recent years, there is still an unmet medical need for a specific population which
have advanced NSCLC and mostly is refractory to existing treatments. NK-1 antagonists are
generally safe and well-tolerated drugs and approved for the treatment of chemotherapy
induced vomiting and nausea. However, the recent findings in preclinical studies and
preliminary results of some case reports have suggested that their potential in cancer
treatment may not be limited to only antiemetic effects.
In addition to the role of NK-1 pathway in emesis, the neuropeptide substance P (SP) binds to
Neurokinin-1(NK-1) receptor and this binding regulates the carcinogenic cell proliferation,
exerts an antiapoptotic effect, stimulates cell migration that leads to invasion and
metastasis of tumor cells and lastly stimulates neoangiogenesis via endothelial cell
proliferation. In this regard, the antitumoral effects of NK-1 antagonists against different
types of cancer are a leading area of research interest and need for further investigation.
Currently, there are three NK-1 receptor antagonists approved by health authorities:
Aprepitant (Emend), its pro-drug, fosaprepitant (Ivemend) and rolapitant (Varubi). All of
these drugs are non-peptid NK antagonists and have lipophilic properties. Therefore, they are
not degraded by peptidase and can cross the blood-brain barrier (4). In addition to the
potential effects of NK-1 antagonists in tumor area, their penetration to central nervous
system may also prevent from or reduce the brain metastasis.
The long term use of aprepitant as off-label is relatively common. In several case reports,
long term use of aprepitant, up to 18 months, was successfully demonstrated in the treatment
of refractory nausea and vomiting due to gastroparesis or other unexplained reasons.
Additionally, in a very recent publication, it was reported that for the nausea and vomiting
associated gastroparesis, long-term off label use of aprepitant was successfully received and
well tolerated by three children (5 to 19 month-old) in the course of allogenic hematopoietic
stem cell transplantation.
In the light of findings in preclinical studies, the antitumor effects of NK-1 antagonists
are dose-dependent and the higher doses than approved antiemetic effective dose are need to
achieve the antitumor activity. For aprepitant which will be used in present study, it has
been recommended >20 mg/kg/day and prolonged use for antitumor activity. In a case report,
prolonged use of standard aprepitant dose in a patient with metastatic breast cancer, had
resulted with a reduction in CA153 tumor marker levels. In another recently published case
report, a patient with lung cancer was treated with combination of aprepitant (1140 mg/day)
and radiotherapy for 45 days, it has been reported that the tumor massed had disappeared
without any side effect related to aprepitant treatment. It is fact that the evidence is not
clear yet and further investigation in clinical trial settings is still needed for the
evaluation of the efficacy and safety of high doses and long-term use of aprepitant,
especially when administered alone to determine its own effect.
Phase:
Phase 2
Details
Lead Sponsor:
ECONiX Araştırma Analiz ve Danışmanlık A.Ş. PlusVitech S.L.
Collaborators:
ECONiX Araştırma Analiz ve Danışmanlık A.Ş. PlusVitech S.L.