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

Prostatic Neoplasms

Antibodies

Immunoglobulins

Altretamine

Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Computed Tomography

Laboratory Biomarker Analysis

Positron Emission Tomography

Recombinant EphB4-HSA Fusion Protein

Cheryl Kefauver, RN

Valerie Mira

Tina Moore

Tanya Dorff, MD

Sarmad Sadeghi, MD

Sarmad Sadeghi

Kristy Massopust

Greg Angstreich, MD

Andrew J Buck

Mamta Parikh, MD

Jane Ledesma

Christina Hopkins

Rahul Parikh, MD

Melissa Vicuna, RN

Christina Shirley, RN

Nicholas Vogelzang, MD

Melani Terry

Lorretta Cecil

Earle Burgess, MD

Jennifer Drake

Michael Devitt, MD

This is a multi-cohort single arm phase II/screening trial of the combination of a fusion protein that binds EphrinB2 and blocks interaction with cell surface EphB receptors (sEphB4-HSA) in combination with an anti-PD1 antibody (MK-7435 / Pembrolizumab) for treatment of patients with specific solid tumors. There will be four cohorts in this trial:

1. Cohort A, phase II 2nd line trial of sEphB4-HSA and pembrolizumab for platinum refractory metastatic urothelial carcinoma.
2. Cohort B, phase II 3rd line trial of sEphB4-HSA and pembrolizumab for platinum refractory metastatic urothelial carcinoma.
3. Cohort C, phase II neoadjuvant trial of sEphB4-HSA and pembrolizumab for locally advanced muscle invasive urothelial carcinoma.
4. Cohort D, phase II neoadjuvant trial of sEphB4-HSA and pembrolizumab for locally advanced prostate cancer.

PRIMARY OBJECTIVES:

I. To describe the toxicity associated with the Pembrolizumab-sEphB4-HSA combination in patients with solid tumors (all Cohorts).

II. To identify a signal of activity for each of 4 cohorts of patients:

1. To measure the overall survival (OS) in patients with urothelial carcinoma who have previously been treated with one line of platinum-based therapy in advanced/metastatic setting (Cohort A).
2. To measure the overall survival (OS) in patients with urothelial carcinoma who have previously been treated with at least two lines of therapy, of which at least one is platinum-based, in advanced/metastatic setting (Cohort B).
3. To measure the pathologic complete response (pCR) rate in patients with newly diagnosed urothelial carcinoma of the bladder (platinum eligible and ineligible) treated in neoadjuvant setting prior to radical cystectomy (Cohort C).
4. To measure the PSA response rate in patients with newly diagnosed prostate cancer in neoadjuvant setting prior to radical prostatectomy (Cohort D).

SECONDARY OBJECTIVES:

I. To measure the progression-free survival (PFS) in Cohorts A and B

II. To measure the disease-free survival (DFS) in Cohorts C and D

III. To measure the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in Cohorts A and B

IV. To measure the pathologic response rate in newly diagnosed prostate cancer patients in neoadjuvant setting prior to radical prostatectomy in Cohort D

TERTIARY OBJECTIVES:

I. To examine programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), programmed cell death 1 ligand 2 (PD-L2) and EPH receptor B4 (EphB4) expression by tumor cells (TC) as well as immune cells (IC)- macrophages and T cells- in tumor tissue and correlate them with ORR, PFS and OS.

II. To examine the tumor tissue T cell frequency (counts), tumor tissue T cell clonality using T cell receptor (TCR) sequencing, and peripheral blood T cell clonality, pre-treatment and post-treatment and correlate these with ORR, PFS and OS.

III. To measure the phenotype of lymphocytes and myeloid derived suppressor cells (MDSC), in pre and post-treatment blood samples and correlate these with ORR, PFS and OS; an extra blood sample for future studies will also be collected and banked.

IV. To examine peripheral blood circulating tumor cells (CTCs) for enumeration and molecular analysis in pre and post-treatment blood samples, and correlate these with ORR, PFS and OS.

V. To collect and bank tumor tissue. VI. To examine the role of adding positron emission tomography (PET) to a contrast computed tomography (CT) for evaluation of response to treatment.

OUTLINE:

Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6-12 weeks.

Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab in Solid Tumors

A Phase II Trial of sEphB4-HSA in Combination With Anti PD1 Antibody Pembrolizumab (MK-3475) for Solid Tumors

All observed toxicities will be summarized in terms of type (organ affected or laboratory determination, severity, and time of onset. Tables will be created to summarize these toxicities and side effects, overall and by course. The proportion of patients who are eligible to begin the 3rd planned cycle will be calculated, using the number of eligible patients who began treatment as the denominator; 95% confidence intervals will be constructed.

The proportion of patients who experience an overall objective response (CR or PR will be calculated as the ratio of the number of eligible patients who experienced the response, divided by the total number of eligible patients who began treatment; 95% confidence intervals will be constructed.

National Cancer Institute (NCI)

University of Southern California

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Quality-of-Life Assessment

Estrella Carballido

This phase II trial studies how well paclitaxel albumin-stabilized nanoparticle formulation maintenance therapy works after cisplatin-based chemotherapy and surgery in treating patients with high-risk bladder cancer. Maintenance therapy, such as paclitaxel albumin-stabilized nanoparticle formulation, can help keep cancer from coming back after it has disappeared following initial chemotherapy.

PRIMARY OBJECTIVES:

I. To evaluate the 6-month progression-free survival (PFS) rate in patients with high risk urothelial carcinoma treated with cisplatin-based neoadjuvant chemotherapy followed by curative intent cystectomy receiving maintenance therapy with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel).

SECONDARY OBJECTIVES:

I. To evaluate overall survival (OS), time to progression and duration of response in patients treated with cisplatin-based neoadjuvant chemotherapy followed by curative intent cystectomy receiving maintenance therapy with nab-paclitaxel.

II. To evaluate the adverse events associated with use of single agent nab-paclitaxel (Abraxane®) in patients with high risk urothelial carcinoma receiving maintenance therapy III. To evaluate Health Related Quality of life (HRQoL) as assessed by the European Organization for Research and Treatment of Care (EORTC) QLQ-C30.

TERTIARY OBJECTIVES:

I. To determine the presence of circulating tumor cells (CTC) in high risk patients with urothelial carcinoma prior to initiation of maintenance therapy (baseline) and after nab-paclitaxel exposure (at cycles 2, 4).

OUTLINE:

Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 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.

Paclitaxel Albumin-Stabilized Nanoparticle Formulation After Cisplatin-Based Chemotherapy and Surgery in Treating Patients With High-Risk Bladder Cancer

Maintenance Nab-Paclitaxel After Cisplatin-Based Neoadjuvant Chemotherapy in Patients With High Risk Bladder Cancer

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated using the approach of Duffy and Santner. Additionally, if some patients are lost to follow-up not having been observed for at least 6 months, an estimate and confidence interval for the 6-month progression-free survival rate incorporating censoring will be computed using the method of Kaplan-Meier (1958).

The distribution of duration of response will be estimated using the method of Kaplan-Meier (1958).

The distribution of survival time will be estimated using the method of Kaplan-Meier (1958).

28 of the 30 items are measured on a 1-4 scale (1=not at all; 4=very much) with the remaining two items (overall health and overall quality of life) scored on a 1-7 numeric analogue scale (1=very poor; 7=excellent). The recall period for the EORTC QLQ-C30 is one week.

The distribution of time to progression will be estimated using the method of Kaplan-Meier (1958).

Mayo Clinic

Vaccines

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.

Radical Cystectomy

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
Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab in Solid Tumors	NCT02717156	Stage IV Bladde... Prostate Cancer Urothelial Carc...	Computed Tomogr... Laboratory Biom... Pembrolizumab Positron Emissi... Recombinant Eph...	18 Years -	University of Southern California
Paclitaxel Albumin-Stabilized Nanoparticle Formulation After Cisplatin-Based Chemotherapy and Surgery in Treating Patients With High-Risk Bladder Cancer	NCT02718742	Recurrent Bladd... Stage IV Bladde...	Laboratory Biom... Paclitaxel Albu... Quality-of-Life...	18 Years -	Mayo Clinic
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
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
Paclitaxel Albumin-Stabilized Nanoparticle Formulation After Cisplatin-Based Chemotherapy and Surgery in Treating Patients With High-Risk Bladder Cancer	NCT02718742	Recurrent Bladd... Stage IV Bladde...	Laboratory Biom... Paclitaxel Albu... Quality-of-Life...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for stage iv bladder urothelial carcinoma