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

NCT01426126 | Completed Phase 2

• 1 other identifier: UOSG-AMC-0702
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Response rate

  Objective tumor response rate according to RECIST criteria V.1.0

  6 months

Secondary Outcomes (3)

• Adverse events

  12 months

• Time to progression

  12 months

• Overall survival

  24 months

Study Arms (1)

Genexol PM

EXPERIMENTAL

Genexol PM intravenous infusion every 3 weeks

Drug: Genexol PM

Interventions

Genexol PM 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)

Genexol PM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Asan Medical Center: lead
• Samsung Medical Center: collaborator
• Kangdong Sacred Heart Hospital: collaborator

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (1)

• 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.

  PMID: 22012004 RESULT

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms; Carcinoma, Transitional Cell

Interventions

genexol-PM

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Jae-Lyun Lee, M.D., Ph.D.

  Asan Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: August 29, 2011
• First Posted: August 31, 2011
• Study Start: December 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2011
• Last Updated: December 7, 2011

Record last verified: 2011-12

Locations

KR (1)