Study of Genexol-PM in Patients With Advanced Urothelial Cancer Previously Treated With Gemcitabine and Platinum

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.

Conditions

• Bladder Cancer
• Ureter Cancer

Interventions

DRUG

Genexol PM

Genexol-PM at a dose of 240 mg/㎡ was diluted in 500 ml of 5% dextrose solution and infused i.v. for 3 hours on day 1. Specialized i.v. infusion sets or in-line filter was not required for the administration. The dose of Genexol-PM was escalated to 300 mg/㎡ from the second cycle when pre-specified criteria were fulfilled (nadir ANC ≥ 1,000/ mm3, nadir platelet count ≥ 100,000/ mm3, and no grade 2 or worse non-hematologic toxicities with the exception of alopecia)

Sponsors & Collaborators

• Samsung Medical Center

  collaborator OTHER

• Kangdong Sacred Heart Hospital

  collaborator OTHER

• Asan Medical Center

  lead OTHER

Principal Investigators

• Jae-Lyun Lee, M.D., Ph.D. · Asan Medical Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-12-31

Primary Completion

2010-07-31

Completion

2011-08-31

Countries

• South Korea

Study Locations