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

Primary Purpose

Bladder Cancer, Ureter Cancer

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Genexol PM
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring urothelial carcinoma, gemcitabine, platinum, refractory, salvage chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Asan Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Genexol PM

Arm Description

Genexol PM intravenous infusion every 3 weeks

Outcomes

Primary Outcome Measures

Response rate
Objective tumor response rate according to RECIST criteria V.1.0

Secondary Outcome Measures

Adverse events
Adverse events according NCI-CTCAE V3.0
Time to progression
Time from the start of treatment to the objective disease progression
Overall survival
Time from the start of treatment to the date of death from any cause

Full Information

First Posted
August 29, 2011
Last Updated
December 6, 2011
Sponsor
Asan Medical Center
Collaborators
Samsung Medical Center, Kangdong Sacred Heart Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01426126
Brief Title
Study of Genexol-PM in Patients With Advanced Urothelial Cancer Previously Treated With Gemcitabine and Platinum
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 Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
Collaborators
Samsung Medical Center, Kangdong Sacred Heart Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Ureter Cancer
Keywords
urothelial carcinoma, gemcitabine, platinum, refractory, salvage chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Genexol PM
Arm Type
Experimental
Arm Description
Genexol PM intravenous infusion every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Genexol PM
Intervention Description
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 Measure Information:
Title
Response rate
Description
Objective tumor response rate according to RECIST criteria V.1.0
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Adverse events
Description
Adverse events according NCI-CTCAE V3.0
Time Frame
12 months
Title
Time to progression
Description
Time from the start of treatment to the objective disease progression
Time Frame
12 months
Title
Overall survival
Description
Time from the start of treatment to the date of death from any cause
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed TCC of the urothelial tract (bladder, renal pelvis, or ureter) Prior exposure to gemcitabine-platinum regimen as either adjuvant or palliative chemotherapy. Unidimensionally measurable disease outside prior radiotherapy ports Age 18 years or older ECOG performance status of 0~2 Life expectancy of at least 3 months Adequate BM function (ANC >1,500/mm3 & Platelet >100,000/mm3) 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) No pre-existing clinically significant grade 2 or greater neuropathy Exclusion Criteria: Pregnant or lactating patients Presence or history of CNS metastasis Patients with prior RT to the axial skeleton within 4 weeks of chemotherapy start to greater than 25% of bone marrow Any preexisting medical condition of sufficient severity to prevent full compliance with the study, including active infection, active cardiac symptoms
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jae-Lyun Lee, M.D., Ph.D.
Organizational Affiliation
Asan Medical Center
Official's Role
Study Director
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
22012004
Citation
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.
Results Reference
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Study of Genexol-PM in Patients With Advanced Urothelial Cancer Previously Treated With Gemcitabine and Platinum

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