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

NCT01639521 | Withdrawn Phase 2 DMC

• 2 other identifiers: 4B-10-5NCI-2012-00961
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Anterior Urethral Cancer; 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; Urethral Cancer Associated With Invasive Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Disease-free survival

  From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years

Study Arms (2)

Arm A (gemcitabine hydrochloride, cisplatin)

EXPERIMENTAL

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.

Drug: cisplatin; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis

Arm B (MVAC)

EXPERIMENTAL

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.

Drug: cisplatin; Drug: methotrexate; Drug: vinblastine; Drug: doxorubicin hydrochloride; Biological: pegfilgrastim; Other: laboratory biomarker analysis

Interventions

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Arm A (gemcitabine hydrochloride, cisplatin); Arm B (MVAC)

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Arm A (gemcitabine hydrochloride, cisplatin)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Arm B (MVAC)

vinblastine DRUG

Given IV

Also known as: Velban, Velsar, VLB

Arm B (MVAC)

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Arm B (MVAC)

pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

Arm B (MVAC)

laboratory biomarker analysis OTHER

Correlative studies

Arm A (gemcitabine hydrochloride, cisplatin); Arm B (MVAC)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urethral Neoplasms; Ureteral Neoplasms

Interventions

Cisplatin; Gemcitabine; Methotrexate; merphos; Vinblastine; Doxorubicin; pegfilgrastim

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; Urethral Diseases; Ureteral Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Tanya Dorff

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2012
• First Posted: July 12, 2012
• Study Start: May 1, 2013
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 29, 2014

Record last verified: 2014-01