Abstract 1511
Background
Angiosarcomas (AS) are rare and aggressive tumors of endothelial cell origin. About half of patients present with a primary cutaneous lesion, most commonly over the scalp. Intravenous (IV) weekly paclitaxel (Pac) is the current accepted standard-of-care in inoperable or progressive disease. Median PFS is 3.8 months. IV Pac is associated with dose-limited toxicities including peripheral neuropathy, development of infusional reactions and anaphylaxis, in part due to the Cremophor EL formulation vehicle. Pac is a P-glycoprotein (P-gp) substrate. Pac is a substrate for the Pgp pump in the intestinal cells which leads to efflux of Pac back into the intestinal lumen, thereby making the drug nonbioavailable when taken orally. ORAXOL is a combination product of 2 separate drugs; oral Pac and a novel Pglycoprotein (Pgp) inhibitor, HM30181 methanesulfonate monohydrate (HM30181A). This allows for intestinal absorption and systemic exposure of Pac. ORAXOL has been studied in bioavailability and bioequivalence studies confirming its safety profile. A multi-center phase III study comparing ORAXOL and IV Pac in women with metastatic breast cancer is on-going. We are currently recruiting patients on a multi-center pilot study to determine the efficacy of ORAXOL in cutaneous AS.
Trial design
This is a multi-center, international, open-label, pilot study to evaluate the activity, safety, and tolerability of ORAXOL in subjects with cutaneous AS who have not been treated previously with taxanes. ORAXOL (15mg oral HM30181A & 205mg/m2 oral Pac) will be administered once daily for 3 consecutive days every week from Weeks 1 through 25; HM30181A is administered 1 hour before oral Pac on dosing days. Subjects who do not have disease progression at the end of treatment period are eligible to continue ORAXOL in the treatment extension phase. Primary objective is to determine the response rate (RR) within 6 months of initiation of treatment. Secondary objectives include (i) safety and tolerability, (ii) PFS and (iii) OS, (iv) duration of- and (v) time to-best response. Up to 25 evaluable subjects across 4 study sites will be enrolled in this study. The first patient has started dosing in December 2018.
Clinical trial identification
NCT03544567.
Editorial acknowledgement
Legal entity responsible for the study
Athenex Inc.
Funding
Athenex Inc.
Disclosure
M.R. Kwan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Cutler: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Kramer: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. W. Chan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. All other authors have declared no conflicts of interest.
Resources from the same session
860 - Dose differential modulation of the autophagic behavior of estrogen expressing breast carcinoma cells
Presenter: Mariam Fouad
Session: Poster Display session 1
Resources:
Abstract
2304 - Synthetic peptide of tumor–associated antigen L6 formulated with polymer-based adjuvant enhances anti-tumor effects in mice
Presenter: Shih-jen Liu
Session: Poster Display session 1
Resources:
Abstract
4419 - Improving detection level of somatic mosaicism in neurofibromatosis type 1
Presenter: Kristina Karandasheva
Session: Poster Display session 1
Resources:
Abstract
5283 - Preclinical pharmacokinetic/pharmacodynamic (PK/PD) relationship of ABN401, a highly selective Met inhibitor, in gastric and non-small-cell lung cancer models
Presenter: JooSeok Kim
Session: Poster Display session 1
Resources:
Abstract
5488 - Transcription factors of Snail family in the regulation of resistance of breast cancer cells to hypoxic conditions
Presenter: Alvina Khamidullina
Session: Poster Display session 1
Resources:
Abstract
5417 - Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumour cells
Presenter: Liliana Mendonça
Session: Poster Display session 1
Resources:
Abstract
5494 - Identification of novel and known FGFR gene fusions in Chinese non-small cell lung cancer
Presenter: Weixin Zhao
Session: Poster Display session 1
Resources:
Abstract
3412 - WNT pathway mutations (APC/CTNNB1) and immune checkpoint inhibitors (ICI) response in metastatic non-small cell lung cancer (NSCLC) patients.
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 1
Resources:
Abstract
1815 - Leukocytosis as a negative prognostic factor in patients with lung cancer: Which subpopulation of leukocytes is responsible?
Presenter: Filip Kohutek
Session: Poster Display session 1
Resources:
Abstract
5022 - Identification of MET gene amplifications using next-generation sequencing in non-small cell lung cancer patients
Presenter: Sergi Clavé
Session: Poster Display session 1
Resources:
Abstract