Study of Genexol-PM in Patients With Advanced Urothelial Cancer Previously Treated With Gemcitabine and Platinum
Status:
Completed
Trial end date:
2011-08-01
Target enrollment:
Participant gender:
Summary
Taxane-based chemotherapy is currently one of the most commonly used regimen for salvage
chemotherapy in advanced urothelial carcinoma. In previously untreated patients, single-agent
paclitaxel, administered in a 24-hour infusion, produced an overall response rate of 42%, and
single-agent docetaxel as a first-line therapy produced response rates of 31% and 45% in 11
patients with impaired renal function. Of the two taxanes, paclitaxel has been studied more
extensively.
Intravenous administration of paclitaxel requires the use of solubilizing agents such as
Cremophor EL (CrEL) due to its hydrophobicity. CrEL often contributes to hypersensitivity
reactions including hypotension or dyspnea with bronchospasm, some of which are major and
potentially life-threatening. Minor allergic reactions such as transient rashes and flushing
also may occur. Despite pretreatment with corticosteroids and histamine antagonists, minor
reactions still occur in 10-44% of all patients, with 1-3% of patients experiencing
potentially fatal reactions. CrEL may also act as a potential cofactor for the development of
peripheral neuropathy. In addition, special infusion sets must be used clinically when
administering CrEL-based paclitaxel.
Genexol-PM (Samyang Co., Seoul, Korea), a form of paclitaxel formulated with sterile,
lyophilized polymeric micells that allow intravenous delivery of paclitaxel without CrEL. The
polymeric micelle formulation is composed of hundreds of low molecular weight, nontoxic, and
biodegradable amphiphilic diblock copolymers which include monomethoxy poly(ethylene
glycol)-block-poly(D,L-lactide), and has a great potential in terms of water solubility, in
vivo stability, and the nanoscopic size (a diameter of 20-50 nm) of the micellar structure.
A phase I study established that Genexol-PM administered at 390 mg/m2 intravenously for 3 h
every 3 weeks was the maximum tolerable dose (MTD) in humans. Dose-limiting toxicities were
neuropathy, myalgia, and neutropenia. No hypersensitivity reactions were observed in any
patients despite the absence of antiallergic premedication. The recommended dosage for phase
II studies was 300 mg/m2.
Based on the promising results of taxane-based chemotherapy and the absence of standard
second-line chemotherapy regimen for advanced urothelial cancer, the investigators designed
phase II study to explore the efficacy and safety of Genexol-PM in advanced urothelial
patients, who previously treated with gemcitabine plus platinum as adjuvant chemotherapy or
1st line therapy for metastatic diseases.
Phase:
Phase 2
Details
Lead Sponsor:
Asan Medical Center
Collaborators:
Kangdong Sacred Heart Hospital Samsung Medical Center