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

NCT ID: NCT01426126

Last Updated: 2011-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2011-08-31

Brief 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

Keywords

urothelial carcinoma; gemcitabine; platinum; refractory; salvage chemotherapy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Genexol PM

Genexol PM intravenous infusion every 3 weeks

Group Type: EXPERIMENTAL

Genexol PM

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed TCC of the urothelial tract (bladder, renal pelvis, or ureter)

2. Prior exposure to gemcitabine-platinum regimen as either adjuvant or palliative chemotherapy.

3. Unidimensionally measurable disease outside prior radiotherapy ports

4. Age 18 years or older

5. ECOG performance status of 0~2

6. Life expectancy of at least 3 months

7. Adequate BM function (ANC >1,500/mm3 & Platelet >100,000/mm3)

8. Adequate hepatic function (Bilirubin no greater than 2 times upper limit of normal (ULN) & AST or ALT no greater than 2.5 times ULN), and renal function (creatinine <1.5 X times ULN)

9. No pre-existing clinically significant grade 2 or greater neuropathy

Exclusion Criteria

1. Pregnant or lactating patients

2. Presence or history of CNS metastasis

3. Patients with prior RT to the axial skeleton within 4 weeks of chemotherapy start to greater than 25% of bone marrow

4. Any preexisting medical condition of sufficient severity to prevent full compliance with the study, including active infection, active cardiac symptoms

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Samsung Medical Center

OTHER

Sponsor Role: collaborator

Kangdong Sacred Heart Hospital

OTHER

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jin-Hee Ahn

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jae-Lyun Lee, M.D., Ph.D.

Role: STUDY_DIRECTOR

Asan Medical Center

Locations

Asan Medical Center

Seoul, , South Korea

Countries

South Korea

References

Lee JL, Ahn JH, Park SH, Lim HY, Kwon JH, Ahn S, Song C, Hong JH, Kim CS, Ahn H. Phase II study of a cremophor-free, polymeric micelle formulation of paclitaxel for patients with advanced urothelial cancer previously treated with gemcitabine and platinum. Invest New Drugs. 2012 Oct;30(5):1984-90. doi: 10.1007/s10637-011-9757-7. Epub 2011 Oct 20.

Reference Type: RESULT

PMID: 22012004 (View on PubMed)

Other Identifiers

UOSG-AMC-0702

Identifier Type: -

Identifier Source: org_study_id