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

January 27, 2014 updated by: University of Southern California

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (gemcitabine hydrochloride, cisplatin)
Patients receive cisplatin 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.
Other: laboratory biomarker analysis
Correlative studies
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • Gemzar
  • gemcitabine
  • dFdC
  • difluorodeoxycytidine hydrochloride
Drug: cisplatin
Given IV
Other Names:
  • CDDP
  • DDP
  • CACP
  • CPDD
Experimental: Arm B (MVAC)
Patients receive methotrexate IV on day 1 and vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV on day 2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Correlative studies
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Drug: cisplatin
Given IV
Other Names:
  • CDDP
  • DDP
  • CACP
  • CPDD
Biological: pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • Neulasta
  • SD-01 sustained duration G-CSF
  • GCSF-SD01
Drug: vinblastine
Given IV
Other Names:
  • Velban
  • Velsar
  • VLB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0
Time Frame: Assessed up to 3 years
80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.
Assessed up to 3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival
Time Frame: From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years
From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Tanya Dorff, University of Southern California

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

July 10, 2012

First Submitted That Met QC Criteria

July 11, 2012

First Posted (Estimate)

July 12, 2012

Study Record Updates

Last Update Posted (Estimate)

January 29, 2014

Last Update Submitted That Met QC Criteria

January 27, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4B-10-5
  • NCI-2012-00961 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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