NCT00942331 · REGISTRY CONDITION SEARCH

Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-06-24

This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with bevacizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Objective Response

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outcome · POSTED

Number of Patients Experiencing Grade 3+ Toxicity

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Patients must have histologically or cytologically documented metastatic or unresectable transitional cell (urothelial) carcinoma of the urinary tract (renal pelvis, ureter, bladder, prostate, or urethra), with metastatic or locally advanced disease (T4b, N2, N3, or M1); patients must not be candidates for potentially curative surgery or radiotherapy * For patients that have had surgical resection prior to study enrollment, residual or unresected disease (measurable and/or unmeasurable) must be evident on post-surgical scans * Prior treatment for transitional cell carcinoma (TCC) * Patients may not have received combination systemic chemotherapy for metastatic disease * For the purposes of this study, radiosensitizing single agent chemotherapy is not considered prior systemic therapy * Prior neoadjuvant or adjuvant systemic chemotherapy is permissible provided the interval from end of therapy to diagnosis of metastatic disease is at least 1 year * \>= 4 weeks since any prior radiation (including palliative) or major surgery and fully recovered * \>= 7 days since any minor surgery such as port placement * \>= 4 weeks since any intravesical therapy * No prior treatment with bevacizumab or other angiogenesis inhibitors * No known history of brain metastases; brain imaging (magnetic resonance imaging \[MRI\]/computed tomography \[CT\]) is not required * No current congestive heart failure; New York Heart Association (NYHA) class II, III or IV * Patients with history of hypertension must be well controlled (\< 150/90) on a regimen of anti-hypertensive therapy * Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range international normalized ratio (INR) (usually between 2 and 3) or be on a stable dose of low molecular weight (LMW) heparin; patients receiving anti-platelet agents are also eligible; in addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible * No significant history of bleeding events or gastrointestinal (GI) perforation * Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible * Patients with a history of GI perforation within 12 months of registration are not eligible * Patients with a history of peritoneal carcinomatosis are not eligible * No arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible * Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study * No serious or non-healing wound, ulcer, or bone fracture * No sensory or motor peripheral neuropathy \>= grade 2 * Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible * Patients that are pregnant or nursing are not eligible; women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours prior to registration * For women of child-bearing potential with an elevated beta-HCG that is believed to be related to cancer and not pregnancy, a negative trans-vaginal ultrasound and gynecological examination are required * Women of child-bearing potential include any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal \[defined as amenorrhea \>= 12 consecutive months; or women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone \[FSH\] level \> 35 mIU/mL); even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (or Karnofsky performance status \[KPS\] \>= 80) * Absolute neutrophil count (ANC) \>= 1,500/uL * Platelet count \>= 100,000/uL * Calculated or measured creatinine clearance \>= 50 mL/minute * Bilirubin =\< 1.25 times upper limits of normal; for patients with Gilbert's disease, =\< 2.5 x upper limit of normal (ULN) is allowed * Aspartate aminotransferase (AST) =\< 2.0 x upper limits of normal * Urine protein to creatinine ratio \< 1.0 or urine protein =\< 1+ or 24-hour urine protein =\< 1 gram
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
intervention Names
Drug: Cisplatin
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
Other: Placebo Administration
label
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
type
ACTIVE_COMPARATOR
description
Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.
intervention Names
Biological: Bevacizumab
Drug: Cisplatin
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
label
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
type
EXPERIMENTAL

interventions

arm Group Labels
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
description
Given IV
name
Bevacizumab
other Names
ABP 215
Anti-VEGF
Anti-VEGF Humanized Monoclonal Antibody
Anti-VEGF Monoclonal Antibody SIBP04
Anti-VEGF rhuMAb
Avastin
Bevacizumab awwb
Bevacizumab Biosimilar ABP 215
Bevacizumab Biosimilar BEVZ92
Bevacizumab Biosimilar BI 695502
Bevacizumab Biosimilar CBT 124
Bevacizumab Biosimilar CT-P16
type
BIOLOGICAL
arm Group Labels
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
description
Given IV
name
Cisplatin
other Names
Abiplatin
Blastolem
Briplatin
CDDP
Cis-diammine-dichloroplatinum
Cis-diamminedichloridoplatinum
Cis-diamminedichloro Platinum (II)
Cis-diamminedichloroplatinum
Cis-dichloroammine Platinum (II)
Cis-platinous Diamine Dichloride
Cis-platinum
Cis-platinum II
type
DRUG
arm Group Labels
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
description
Given IV
name
Gemcitabine Hydrochloride
other Names
dFdCyd
Difluorodeoxycytidine Hydrochloride
FF 10832
FF-10832
FF10832
Gemcitabine HCI
Gemzar
LY-188011
LY188011
type
DRUG
arm Group Labels
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
Arm II (gemcitabine hydrochloride, cisplatin, bevacizumab)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Arm I (gemcitabine hydrochloride, cisplatin, placebo)
description
Given IV
name
Placebo Administration
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 506
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.The stratified log-rank statistic will be the primary analysis to compare the two treatment arms on OS with the stratification factors: presence of visceral metastases (no, yes) and prior chemotherapy (no, yes). In addition, the proportional hazards model will be used to assess the importance of the treatment arm adjusting on patient characteristics, stratification variables and other important covariates in predicting OS.
measure
Overall Survival (OS)
time Frame
From date of randomization to date of death due to any cause, assessed up to 7 years

secondary Outcomes

description
The primary analysis of PFS will be a two-sided stratified log-rank test comparing arm A and arm B. The stratification factors will consist of the two stratification factors used for patient randomization: prior nephrectomy (yes vs. no) and Motzer score (0 vs. 1-2 vs. 3+). Results from unstratified log-rank tests will also be provided. Kaplan-Meier methodology will be used to estimate median PFS for each treatment arm.
measure
Progression-free Survival (PFS)
time Frame
From the date of randomization to date of progression or death due to any cause, whichever occurs first, assessed up to 7 years
description
Objective response is defined as confirmed complete and partial responses using Response Evaluation Criteria in Solid Tumors criteria. A complete response (CR) is defined as a disappearance of all target lesions. A partial response (PR) is defined as having at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum. In each arm, the number of patients reporting a CR or PR was divided by the number of patients evaluable in each arm to obtain the proportion.
measure
Objective Response
time Frame
Up to 7 years
description
The number of patients experiencing grade 3 or higher toxicity (adverse events considered at least possibly related to treatment) is reported below.
measure
Number of Patients Experiencing Grade 3+ Toxicity
time Frame
Up to 7 years

Full study description

brief Summary: This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with bevacizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.
detailed Description: PRIMARY OBJECTIVES: I. To determine if patients with advanced transitional cell carcinoma treated with bevacizumab, gemcitabine hydrochloride (gemcitabine) and cisplatin will have increased overall survival when compared to patients treated with gemcitabine, cisplatin, and placebo. SECONDARY OBJECTIVES: I. To compare the progression-free survival of these two regimens in patients with advanced transitional cell carcinoma. II. To compare the proportion of patients who experience an objective response on each regimen. III. To compare the grade 3 and greater toxicities in patients treated on the two regimens. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, cisplatin IV, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 7 years.

Source references

references

citation
Iyer G, Choi W, Luo B, Carvalho F, Hanlon T, Reis H, Guercio BJ, Fong M, Mountain J, Feng M, Regazzi AM, McCart L, Wen Y, Al-Ahmadie H, Mouw KW, Van Allen EM, Bellmunt J, Dreicer R, Flaig TW, Halabi S, McConkey DJ, Rosenberg JE. Relationship Among DNA Damage Response Gene Alterations, Molecular Subtypes, and Survival Outcomes in Patients With Metastatic Bladder Cancer Treated on CALGB 90601. JCO Precis Oncol. 2025 Jul;9:e2400938. doi: 10.1200/PO-24-00938. Epub 2025 Jul 1.
pmid
40591902
type
DERIVED
citation
Guercio BJ, Whiting K, Shah RH, Ballman KV, Halabi S, Regazzi AM, Milbank JH, Bajorin DF, Beltran H, Morris MJ, Solit DB, Berger MF, Iyer G, Seshan V, Rosenberg JE. Circulating Tumor DNA and Response to Cisplatin-based Chemotherapy in Patients with Metastatic Urothelial Carcinoma Enrolled in CALGB 90601 (Alliance). Eur Urol Open Sci. 2025 Apr 7;75:80-88. doi: 10.1016/j.euros.2025.03.009. eCollection 2025 May.
pmid
40256659
type
DERIVED
citation
Rosenberg JE, Ballman KA, Halabi S, Atherton PJ, Mortazavi A, Sweeney C, Stadler WM, Teply BA, Picus J, Tagawa ST, Katragadda S, Vaena D, Misleh J, Hoimes C, Plimack ER, Flaig TW, Dreicer R, Bajorin D, Hahn O, Small EJ, Morris MJ. Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance). J Clin Oncol. 2021 Aug 1;39(22):2486-2496. doi: 10.1200/JCO.21.00286. Epub 2021 May 14.
pmid
33989025
type
DERIVED