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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01426126
Recruitment Status : Completed
First Posted : August 31, 2011
Last Update Posted : December 7, 2011
Samsung Medical Center
Kangdong Sacred Heart Hospital
Information provided by (Responsible Party):
Jin-Hee Ahn, Asan Medical Center

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.

Condition or disease Intervention/treatment Phase
Bladder Cancer Ureter Cancer Drug: Genexol PM Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Genexol-PM, a Cremophor-free, Polymeric Micelle Formulation of Paclitaxel for Patients With Advanced Urothelial Cancer Previously Treated With Gemcitabine and Platinum
Study Start Date : December 2007
Actual Primary Completion Date : July 2010
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Gemcitabine
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Genexol PM
Genexol PM intravenous infusion every 3 weeks
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)

Primary Outcome Measures :
  1. Response rate [ Time Frame: 6 months ]
    Objective tumor response rate according to RECIST criteria V.1.0

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 12 months ]
    Adverse events according NCI-CTCAE V3.0

  2. Time to progression [ Time Frame: 12 months ]
    Time from the start of treatment to the objective disease progression

  3. Overall survival [ Time Frame: 24 months ]
    Time from the start of treatment to the date of death from any cause

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01426126

Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Samsung Medical Center
Kangdong Sacred Heart Hospital
Study Director: Jae-Lyun Lee, M.D., Ph.D. Asan Medical Center

Publications of Results:
Responsible Party: Jin-Hee Ahn, Associate professor, Asan Medical Center Identifier: NCT01426126     History of Changes
Other Study ID Numbers: UOSG-AMC-0702
First Posted: August 31, 2011    Key Record Dates
Last Update Posted: December 7, 2011
Last Verified: December 2011

Keywords provided by Jin-Hee Ahn, Asan Medical Center:
urothelial carcinoma
salvage chemotherapy

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Ureteral Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs