Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Recurrence

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urethral Neoplasms

Kidney Neoplasms

Ureteral Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urethral Diseases

Urologic Diseases

Male Urogenital Diseases

Urinary Bladder Diseases

Kidney Diseases

Ureteral Diseases

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Docetaxel

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

pembrolizumab IV over 30 minutes on day 1 and docetaxel IV over 60 minutes on day 1.

pembrolizumab IV as in Arm A and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8.

Gemcitabine Hydrochloride

Primo Lara

This phase I trial studies the side effects and best dose of pembrolizumab when given together with docetaxel or gemcitabine hydrochloride in treating patients with previously treated urothelial cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or that has spread from the primary site (place where it started) to other places in the body (metastatic). Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as docetaxel and gemcitabine hydrochloride, 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. Giving pembrolizumab together with docetaxel or gemcitabine hydrochloride may be a better treatment for urothelial cancer.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of MK-3475 (pembrolizumab) when given in combination with docetaxel or gemcitabine (gemcitabine hydrochloride) in patients with advanced or metastatic platinum-treated urothelial cancer.

SECONDARY OBJECTIVES:

I. To assess in a preliminary manner the efficacy of this combination (overall response rate and progression free survival).

II. To determine in an exploratory manner programmed death (PD)-ligand (L)1 expression in archival tumor specimens and to correlate this with patient outcomes.

OUTLINE: This is a dose-escalation study of pembrolizumab. Patients are assigned to 1 of 2 treatment arms. (Patients who had received prior gemcitabine hydrochloride/cisplatin or gemcitabine hydrochloride/carboplatin \[GC\] or methotrexate, vinblastine sulfate, adriamycin, and cisplatin \[MVAC\] therapy are assigned to Arm A).

ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and docetaxel IV over 60 minutes on day 1.

ARM B: Patients receive pembrolizumab IV as in Arm A and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8.

In both arms, treatment repeats every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 6 months.

Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer

Feasibility Trial of MK3475 + Docetaxel or Gemcitabine in Platinum Pre-treated Urothelial Cancer

Will be summarized descriptively by tables of numbers and percent of patients experiencing adverse events, overall and by type, grade, seriousness, duration, action taken, and assessment of relation to pembrolizumab or docetaxel or gemcitabine hydrochloride.

The number and proportion experiencing complete response, partial response, stable disease, or progressive disease will be summarized separately for each study arm.

Will be summarized graphically by Kaplan-Meier curves and descriptively by a corresponding life-table approach to allow for possible censored data.

The relation of PD-L1 expression at baseline to outcome (ORR and PFS) will be summarized descriptively in exploratory analyses, separately for each study arm. Descriptive associations with ORR will be summarized by the means and standard deviations for responders vs. non-responders, and graphically by dot plots of PD-L1 expression for responders and non-responders. Descriptive associations with PFS will be summarized by Kaplan-Meier plots comparing PFS for high and low PD-L1 expression.

Merck Sharp & Dohme LLC

University of California, Davis

Questionnaire Administration

Radical Cystectomy

Mihir Desai

This randomized phase II trial studies how well robotic radical cystectomy (RRC) or open radical cystectomy (ORC) works in treating patients with bladder cancer. Cystectomy is a surgical procedure to remove all or part of the bladder (the organ that holds urine) or to remove a cyst (a sac or capsule in the body). In RRC, the the surgeon makes small cuts in the abdomen and uses a thin, lighted instrument with a camera attached called a scope. With the help of a robot, the surgeon removes the bladder and other nearby structures. In ORC, the surgeon makes a cut into the lower abdomen to expose the urinary tract in order to remove the bladder and nearby structures. It is not yet known whether RRC or ORC has fewer complications, better quality of life, and faster recovery time in treating patients with bladder cancer.

PRIMARY OBJECTIVES:

I. To compare RRC to ORC in terms of the difference in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core (QLQC)30 quality of life instrument assessed at baseline to day 30 after radical cystectomy (RC).

II. To compare RRC to ORC in terms of the 90-day high-grade complication rate (where high grade is defined as Clavien-Dindo grade 3-5).

III. To compare the peri-operative cost of the RC procedure, as defined as from the day of hospital admission to the day of hospital discharge.

SECONDARY OBJECTIVES:

I. To estimate the differences between RRC and ORC in terms of the following quality of life outcomes: Narcotic requirements prior to RC, during hospital stay and on days 7, 14, 30, 6 weeks, and 3, 6, 9 and 12 months; Visual Analog Scale (VAS) pain score prior to RC and on days 7, 14, 30, 6 weeks, and 3, 6, 9 and 12 months; the EORTC-QLQ-30 prior to RC and at 3, 6, 9, and 12 months; the bladder cancer index (BCI) at 30 days and 3, 6, 9, and 12 months; the Sexual Health Inventory for Men (SHIM) prior to RC and at 3, 6, 9, and 12 months; the World Health Organization (WHO) Quality of Life (QOL) questionnaire prior to RC and at 30 days and 3, 6, 9, and 12 months.

II. To estimate the differences between RRC and ORC in terms of the following surgical and complication outcomes: all complications occurring intraoperatively, during postoperative hospitalization and during the 90 days post cystectomy assessed at 7, 14, and 30 days; at 6 weeks and at 3 months-graded according to the Clavien-Dindo classification; all complications, all grade 3+ complications, and all grade 4+ complications; time to oral intake; estimated blood loss during surgery, number of transfusions on the day of surgery; drop in hematocrit at 24 hours; lymph node yield; and positive surgical margin.

III. To estimate the differences between RRC and ORC in terms of the following cost-related outcomes: operation room time; number of disposables used; pharmacy costs; length of hospital stay; admission to intensive care unit (ICU) prior to discharge \& length of stay in ICU; number of hospital readmissions within 30 and 90 days (3 months); necessary tests/procedures to treat complications during hospitalization and within 30 and 90 days.

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

ARM I: Patients undergo RRC at day 0.

ARM II: Patients undergo ORC at day 0.

After completion of study treatment, patients are followed up at 7 days, 30 days, 6 weeks, and at 3, 6, 9, and 12 months.

Robotic or Open Radical Cystectomy in Treating Patients With Bladder Cancer

Prospective Randomized Comparison of Robotic Versus Open Radical Cystectomy

The results for the two arms will be summarized using graphical methods and standard descriptive statistics. Means (or medians) and associated 95% confidence intervals-for each arm separately and for the difference-will be used to display the patterns. For QoL variables that are assessed at multiple times post cystectomy, regression methods that accommodate repeated measures will be used to assess patterns over time. Analyses will compare the two arms using general linear regression models and stratifying for the four variables used for stratification prior to randomization.

National Cancer Institute (NCI)

University of Southern California

Vaccines

Cisplatin

Immunologic Factors

NEOADJUVANT PHASE: Patients receive gemcitabine hydrochloride IV on days 1 and 8, AGS-003-BLD ID on day 1, and cisplatin IV on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive AGS-003-BLD ID on day 1. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients undergo cystectomy during course 8.

ADJUVANT PHASE: Patients continue AGS-003-BLD ID on day 1 of course 9. Treatment repeats every 12 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Tumor Cell-Derived Vaccine Therapy

Brian Costello

This pilot clinical trial studies how well gemcitabine hydrochloride, cisplatin, and AGS-003-BLD work in treating patients with bladder cancer that has spread to the muscle and who are undergoing surgery. 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. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells. Giving gemcitabine hydrochloride, cisplatin, and AGS-003-BLD before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed by surgery.

PRIMARY OBJECTIVES:

I. To assess the immunogenicity of AGS-003-BLD in subjects with muscle invasive bladder cancer.

SECONDARY OBJECTIVES:

I. To assess 1-year disease-free survival rate of patients with muscle-invasive bladder cancer who receive cisplatin/gemcitabine chemotherapy plus AGS-003-BLD.

II. To determine the time to first metastatic lesion. III. To explore the disease-free and overall survival of patients treated with this treatment combination.

IV. To evaluate the pathologic complete response (pCR) rate and identify any activity of this treatment combination.

V. To evaluate toxicities and tolerability associated with this treatment combination.

VI. To assess the success rate of tumor procurement and AGS-003-BLD production of \>= 5 doses.

TERTIARY OBJECTIVES:

I. To evaluate the relationships between pathologic complete response with the change in CD28+ T cell levels.

II. To evaluate the change in frequency of CD11a highPD-1+ CD8+ T cells (and their expression of Bim) in peripheral blood.

OUTLINE:

NEOADJUVANT PHASE: Patients receive gemcitabine hydrochloride intravenously (IV) on days 1 and 8, AGS-003-BLD intradermally (ID) on day 1, and cisplatin IV on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive AGS-003-BLD ID on day 1. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients undergo cystectomy during course 8.

ADJUVANT PHASE: Patients continue AGS-003-BLD ID on day 1 of course 9. Treatment repeats every 12 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Gemcitabine Hydrochloride, Cisplatin, and AGS-003-BLD in Treating Patients With Muscle-Invasive Bladder Cancer Undergoing Surgery

Pilot Study of Gemcitabine and Cisplatin Plus AGS-003-BLD in Patients With Muscle-Invasive Bladder Cancer Undergoing Neoadjuvant Cisplatin-Based Chemotherapy

Descriptive statistics (mean, sd, median, iqr) and longitudinal plots (raw value, change, and change in percentage) will be used to summarize the correlative endpoints. Further analysis will depend on the amount of data received and will be mainly exploratory.

Descriptive statistics (mean, standard deviation \[sd\], median, interquartile range \[iqr\]) will be used to summarize change from baseline in the frequency of CD11a high PD-1+ CD8+ T cells following five doses of AGS-003-BLD.

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns.

Descriptive statistics (frequency table) and histogram will be used to summarize the success rate.

Descriptive statistics (frequency table) and histogram will be used to summarize the pathologic complete response rate.

Will be estimated using the Kaplan-Meier method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer	NCT02437370	Metastatic Urot... Recurrent Bladd... Recurrent Uroth... Regional Urothe... Stage III Bladd... Stage III Ureth... Stage IV Bladde... Stage IV Urethr... Urethral Urothe...	Pembrolizumab Docetaxel Gemcitabine Hyd...	18 Years -	University of California, Davis
Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer	NCT02437370	Metastatic Urot... Recurrent Bladd... Recurrent Uroth... Regional Urothe... Stage III Bladd... Stage III Ureth... Stage IV Bladde... Stage IV Urethr... Urethral Urothe...	Pembrolizumab Docetaxel Gemcitabine Hyd...	18 Years -	University of California, Davis
Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer	NCT02437370	Metastatic Urot... Recurrent Bladd... Recurrent Uroth... Regional Urothe... Stage III Bladd... Stage III Ureth... Stage IV Bladde... Stage IV Urethr... Urethral Urothe...	Pembrolizumab Docetaxel Gemcitabine Hyd...	18 Years -	University of California, Davis
Robotic or Open Radical Cystectomy in Treating Patients With Bladder Cancer	NCT02699853	Stage 0is Bladd... Stage I Bladder... Stage II Bladde... Stage III Bladd...	Questionnaire A... Radical Cystect... Radical Cystect...	-	University of Southern California
Gemcitabine Hydrochloride, Cisplatin, and AGS-003-BLD in Treating Patients With Muscle-Invasive Bladder Cancer Undergoing Surgery	NCT02944357	Infiltrating Bl... Stage II Bladde... Stage III Bladd... Stage IV Bladde...	Cisplatin Gemcitabine Hyd... Radical Cystect... Tumor Cell-Deri...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for stage iii bladder urothelial carcinoma