Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urethral Neoplasms

Ureteral Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urethral Diseases

Urologic Diseases

Male Urogenital Diseases

Ureteral Diseases

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Halichondrin B

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Eribulin Mesylate

Gemcitabine Hydrochloride

Sarmad Sadeghi

This phase II trial studies how well gemcitabine hydrochloride and eribulin mesylate work in treating patients with bladder cancer that has spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and eribulin mesylate, 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.

PRIMARY OBJECTIVES:

I. To estimate the objective response rate of gemcitabine (gemcitabine hydrochloride)-eribulin (eribulin mesylate) (GE) when given to cisplatin ineligible patients with advanced or unresectable urothelial carcinoma who have not received any prior chemotherapy for the advanced disease.

SECONDARY OBJECTIVES:

I. To estimate the median progression-free survival (PFS). II. To summarize the toxicity profile (using Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4 criteria) of the GE regimen in these patients.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 36 months.

Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery

Phase II Trial of Gemcitabine-Eribulin (GE) in Cisplatin Ineligible Patients With Advanced or Unresectable Urothelial Carcinoma of the Bladder

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Observed Overall Response Rate = Number of patients who experienced a confirmed CR or PR divided by the number of eligible patients who began treatment.

Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Estimated using the product-limit method of Kaplan and Meier.

Toxicities that Occurred in 10% or More of Patients or At Least Once as a Grade 3+ Adverse Event (excluding those toxicities classified as "unrelated" or "unlikely related" to study drugs). Toxicities graded using CTCAEv4 criteria.

National Cancer Institute (NCI)

"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Patients receive 1000mg/m\^2 gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and 1.4mg/m\^2 eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Eribulin Mesylate: Given IV

Gemcitabine Hydrochloride: Given IV

Treatment (Eribulin Mesylate and Gemcitabine Hydrochloride)

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

United States

Region of Enrollment

Paul Frankel, Ph.D.

Observed Overall Response Rate

Progression-free Survival

Overall Survival

Grade 1 or 2 : Anemia

Grade 1 or 2 : Febrile neutropenia

Grade 1 or 2 : Thrombotic microangiopathy

Grade 1 or 2 : Chest pain - cardiac

Grade 1 or 2 : Heart failure

Grade 1 or 2 : Colitis

Grade 1 or 2 : Constipation

Grade 1 or 2 : Diarrhea

Grade 1 or 2 : Dry Mouth

Grade 1 or 2 : Mucositis oral

Grade 1 or 2 : Nausea

Grade 1 or 2 : Vomiting

Grade 1 or 2 : Edema

Grade 1 or 2 : Fatigue

Grade 1 or 2 : Fever

Grade 1 or 2 : Appendicitis perforated

Grade 1 or 2 : Lung infection

Grade 1 or 2 : Sepsis

Grade 1 or 2 : Upper respiratory infection

Grade 1 or 2 : Urinary Tract Infection

Grade 1 or 2 : Electrocardiogram QT

Grade 1 or 2 : Weight Loss

Grade 1 or 2 : Lymphocyte Count Decreased

Grade 1 or 2 : Neutrophil Count Decreased

Grade 1 or 2 : Platelet Count Decreased

Grade 1 or 2 : White Blood Cell Decreased

Grade 1 or 2 : INR increased

Grade 1 or 2 : Alanine Aminotransferase Increased

Grade 1 or 2 : Aspartate Aminotransferase Incr

Grade 1 or 2 : Creatinine Increased

Grade 1 or 2 : Anorexia

Grade 1 or 2 : Hyperglycemia

Grade 1 or 2 : Dehydration

Grade 1 or 2 : Hypoalbuminemia

Grade 1 or 2 : Hypocalcemia

Grade 1 or 2 : Hypokalemia

Grade 1 or 2 : Hypomagnesemia

Grade 1 or 2 : Hyponatremia

Grade 1 or 2 : Hypophosphatemia

Grade 1 or 2 : Generalized Muscle Weakness

Grade 1 or 2 : Grip Weakness

Grade 1 or 2 : Pain in Extremity

Grade 1 or 2 : Dizziness

Grade 1 or 2 : Dysgeusia

Grade 1 or 2 : Paresthesia

Grade 1 or 2 : Peripheral Sensory Neuropathy

Grade 1 or 2 : Insomnia

Grade 1 or 2 : Dyspnea

Grade 1 or 2 : Pneumonitis

Grade 1 or 2 : Sore Throat

Grade 1 or 2 : Alopecia

Grade 1 or 2 : Hypotension

Grade 1 or 2 : Thromboembolic event

Grade 3 or 4 : Anemia

Grade 3 or 4 : Febrile neutropenia

Grade 3 or 4 : Thrombotic microangiopathy

Grade 3 or 4 : Chest pain - cardiac

Grade 3 or 4 : Heart failure

Grade 3 or 4 : Colitis

Grade 3 or 4 : Constipation

Grade 3 or 4 : Diarrhea

Grade 3 or 4 : Dry Mouth

Grade 3 or 4 : Mucositis oral

Grade 3 or 4 : Nausea

Grade 3 or 4 : Vomiting

Grade 3 or 4 : Edema

Grade 3 or 4 : Fatigue

Grade 3 or 4 : Fever

Grade 3 or 4 : Appendicitis perforated

Grade 3 or 4 : Lung infection

Grade 3 or 4 : Sepsis

Grade 3 or 4 : Upper respiratory infection

Grade 3 or 4 : Urinary Tract Infection

Grade 3 or 4 : Electrocardiogram QT

Grade 3 or 4 : Weight Loss

Grade 3 or 4 : Lymphocyte Count Decreased

Grade 3 or 4 : Neutrophil Count Decreased

Grade 3 or 4 : Platelet Count Decreased

Grade 3 or 4 : White Blood Cell Decreased

Grade 3 or 4 : INR increased

Grade 3 or 4 : Alanine Aminotransferase Increased

Grade 3 or 4 : Aspartate Aminotransferase Incr

Grade 3 or 4 : Creatinine Increased

Grade 3 or 4 : Anorexia

Grade 3 or 4 : Hyperglycemia

Grade 3 or 4 : Dehydration

Grade 3 or 4 : Hypoalbuminemia

Grade 3 or 4 : Hypocalcemia

Grade 3 or 4 : Hypokalemia

Grade 3 or 4 : Hypomagnesemia

Grade 3 or 4 : Hyponatremia

Grade 3 or 4 : Hypophosphatemia

Grade 3 or 4 : Generalized Muscle Weakness

Grade 3 or 4 : Grip Weakness

Grade 3 or 4 : Pain in Extremity

Grade 3 or 4 : Dizziness

Grade 3 or 4 : Dysgeusia

Grade 3 or 4 : Paresthesia

Grade 3 or 4 : Peripheral Sensory Neuropathy

Grade 3 or 4 : Insomnia

Incidence of Adverse Events.

Overall Study

Hydronephrosis

Pelvic Neoplasms

Kidney Neoplasms

Kidney Diseases

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Tremelimumab

Ipilimumab

Antineoplastic Agents, Immunological

Immunologic Factors

Immune Checkpoint Inhibitors

Patients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1 of weeks 1 and 4. Beginning 4-6 weeks after the last infusion, patients undergo cystectomy with pelvic lymph node dissection surgery.

Undergo cystectomy with pelvic lymph node dissection

Therapeutic Conventional Surgery

Jianjun Gao

This pilot phase I trial studies the side effects of durvalumab and tremelimumab in treating patients with muscle-invasive, high-risk urothelial cancer that cannot be treated with cisplatin-based therapy before surgery. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer who are ineligible for neoadjuvant cisplatin-containing chemotherapies.

SECONDARY OBJECTIVES:

I. To assess immunologic/molecular responses (e.g. peripheral blood cluster of differentiation \[CD\] 4+inducible T-cell co-stimulator \[ICOS\]+ T cells) to durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer who are ineligible for neoadjuvant cisplatin-containing chemotherapies.

II. To evaluate pathologic T0 rate after neoadjuvant treatment with durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer comparing to historical data (about 10% in patients with high-risk disease).

III. To evaluate relapse-free survival (RFS) and overall survival (OS).

OUTLINE:

Patients receive tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1 of weeks 1 and 4. Beginning 4-6 weeks after the last infusion, patients undergo cystectomy with pelvic lymph node dissection surgery.

After completion of study treatment, patients are followed up at 90 days, and then every 3 months for up 1 year.

Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery

A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 (Tremelimumab) in Patients With Muscle-Invasive, High-Risk Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Neoadjuvant Chemotherapy

M.D. Anderson Cancer Center

Prostatic Neoplasms

Bevacizumab

Endothelial Growth Factors

Mitogens

Angiogenesis Inhibitors

Growth Inhibitors

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.

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.

Laboratory Biomarker Analysis

Placebo Administration

Jonathan E Rosenberg

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.

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.

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

A Randomized Double-Blinded Phase III Study Comparing Gemcitabine, Cisplatin, and Bevacizumab to Gemcitabine, Cisplatin, and Placebo in Patients With Advanced Transitional Cell Carcinoma

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.

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.

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.

The number of patients experiencing grade 3 or higher toxicity (adverse events considered at least possibly related to treatment) is reported below.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery	NCT02178241	Metastatic Uret... Metastatic Uret... Stage III Bladd... Stage III Urete... Stage III Ureth... Stage IV Bladde... Stage IV Ureter... Stage IV Urethr... Ureter Urotheli... Urethral Urothe...	Eribulin Mesyla... Gemcitabine Hyd...	18 Years -	National Cancer Institute (NCI)
Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery	NCT02812420	Hydronephrosis Infiltrating Bl... Infiltrating Bl... Infiltrating Bl... Infiltrating Re... Renal Pelvis Ur... Stage II Bladde... Stage II Renal ... Stage II Ureter... Stage II Urethr... Stage III Bladd... Stage III Renal... Stage III Urete... Stage III Ureth... Stage IV Renal ... Stage IV Ureter... Stage IV Urethr... Ureter Urotheli... Urethral Urothe...	Durvalumab Therapeutic Con... Tremelimumab	18 Years -	M.D. Anderson Cancer Center
Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery	NCT02178241	Metastatic Uret... Metastatic Uret... Stage III Bladd... Stage III Urete... Stage III Ureth... Stage IV Bladde... Stage IV Ureter... Stage IV Urethr... Ureter Urotheli... Urethral Urothe...	Eribulin Mesyla... Gemcitabine Hyd...	18 Years -	National Cancer Institute (NCI)
Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer	NCT00942331	Advanced Urothe... Metastatic Blad... Metastatic Pros... Metastatic Rena... Metastatic Uret... Metastatic Uret... Metastatic Urot... Stage IV Bladde... Stage IV Prosta... Stage IV Renal ... Stage IV Ureter... Stage IV Urethr... Unresectable Ur...	Bevacizumab Cisplatin Gemcitabine Hyd... Laboratory Biom... Placebo Adminis...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iv urethral cancer ajcc v7