Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer

Transitional Cell Carcinoma of the Bladder Clinical Trial

Official title:

Randomized Phase II Trial Of Adjuvant Chemotherapy For Urothelial Carcinoma Comparing GC To Dose-Dense MVAC

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01639521
• Other study ID #: 4B-10-5
• Secondary ID: NCI-2012-00961
• Status: Withdrawn
• Phase: Phase 2
• First received: July 10, 2012
• Last updated: January 27, 2014
• Start date: May 2013
• Est. completion date: May 2013

Study information

• Verified date: January 2014
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

This study is about two chemotherapy study drug combinations (regimens) that are used for urothelial (bladder or upper urinary tract) cancer. Both study drug regimens, gemcitabine (gemcitabine hydrochloride) plus cisplatin, and high-dose-intensity MVAC (methotrexate, vinblastine, doxorubicin plus cisplatin), are standard chemotherapy regimens. Both regimens are used to treat people with urothelial cancer that has spread to other organs. Both study drug regimens have been proven to be effective in lowering the risk of the cancer coming back, but it is not known which regimen is the best. This study hopes to learn whether there is a difference in the effectiveness and side effects of these two study drug regimens when they are given to people who have had their urothelial cancer completely removed.

Description:

PRIMARY OBJECTIVES

To estimate the difference in the rate of unacceptable toxicity for dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin (GC) in the adjuvant treatment of urothelial cancer.

SECONDARY OBJECTIVES

To compare rates of disease recurrence at 3 years between dose-dense MVAC and GC.

To determine whether molecular markers excision repair cross-complementing-1 (ERCC-1) ribonucleoside-diphosphate reductase M-1 (RRM-1), breast cancer 1 (BRCA1) topoisomerase 2-alpha (Top2A) and protein 53 (p53) can predict those patients more likely to benefit from chemotherapy.

To investigate the potential utility of cytidine deaminase (CDA), ERCC-1, xeroderma pigmentosum group D (XPD), glutathione S-transferase P-1 (GSTP-1) and glutathione S-transferase M-1 (GSTM-1) as molecular markers which predict occurrence of significant toxicity during adjuvant chemotherapy for urothelial cancer.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive cisplatin intravenously (IV) on day 1 and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive methotrexate IV on day 1, vinblastine IV, doxorubicin hydrochloride IV, cisplatin IV on day 2 and pegfilgrastim subcutaneously (SC) on day 3. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed high-grade urothelial carcinoma, stage T3bN0, T4N0 or any T stage with lymph node involvement, completely resected; including upper tract urothelial carcinoma

• The dominant histology must be transitional cell or urothelial but foci of other histologies less than 20 percent of the total tumor volume are permitted

• Absence of metastatic disease on radiographic imaging

• Patients must be enrolled and able to start treatment within 90 days of radical cystectomy or radical nephrectomy

• Creatinine less than institutional upper limit of normal (ULN) or clearance greater or equal to 50 mL/min (may be calculated by Cockcroft-Gault formula or measured from 24-hour urine collection)

• Serum total bilirubin less or equal to 1.5 x ULN (except for patients with Gilbert's)

• Alkaline phosphatase less or equal to 2.5 x ULN

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) less or equal to 2.5 x ULN

• White blood cells (WBC) greater or equal to 3000

• Absolute neutrophil count (ANC) greater or equal to 1500

• Hemoglobin (Hb) greater or equal to 9

• Platelets greater or equal to 100,000

• Normal left ventricular ejection fraction, by echocardiogram or multi gated acquisition scan (MUGA)

• Patients must be recovered from surgery

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Willing and able to provide informed consent

• Willingness to use barrier contraception during study period

Exclusion Criteria:

• The presence of significant pleural effusion or ascites

• Prior systemic chemotherapy for urothelial carcinoma including neoadjuvant chemotherapy (prior intravesical therapy is permitted)

• History of malignancy within preceding 5 years, aside from non-melanoma skin cancer or previously treated or incidentally detected prostate cancer with undetectable PSA (after radical cystectomy or prostate cancer therapy)

• Peripheral neuropathy greater than grade 1

• The presence of active heart disease such as congestive heart failure or unstable angina

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anterior Urethral Cancer
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Localized Transitional Cell Cancer of the Renal Pelvis and Ureter
• Posterior Urethral Cancer
• Recurrent Bladder Cancer
• Recurrent Urethral Cancer
• Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
• Stage III Bladder Cancer
• Transitional Cell Carcinoma of the Bladder
• Ureter Cancer
• Ureteral Neoplasms
• Urethral Cancer Associated With Invasive Bladder Cancer
• Urethral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• cisplatin
Given IV
• gemcitabine hydrochloride
Given IV
• methotrexate
Given IV
• vinblastine
Given IV
• doxorubicin hydrochloride
Given IV

Biological:
• pegfilgrastim
Given SC

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0	80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.	Assessed up to 3 years	Yes
Secondary	Disease-free survival		From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years	No