Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Carcinoma, Renal Cell

Lung Neoplasms

Lymphoma

Urinary Bladder Neoplasms

Hodgkin Disease

Melanoma, Cutaneous Malignant

Squamous Cell Carcinoma of Head and Neck

Skin Neoplasms

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplasms, Squamous Cell

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Kidney Neoplasms

Kidney Diseases

Head and Neck Neoplasms

Renal Cell Carcinoma

Lymphosarcoma

Clear Cell Renal Cell Carcinoma

Hodgkin Lymphoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Pembrolizumab

Antibodies

Immunoglobulins

Enzyme Inhibitors

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive trigriluzole PO QOD, BID, QAM or QHS on days -14 to -1. Patients then receive nivolumab IV over 60 minutes every 2 weeks beginning week 1 and trigriluzole PO QOD, BID, QAM or QHS. Once the MTD of trigriluzole with nivolumab is identified, patients receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Enzyme Inhibitor Therapy

Laboratory Biomarker Analysis

Biren Saraiya

This phase I trial studies the best dose and side effects of trigriluzole in combination with nivolumab and pembrolizumab in treating patients with solid malignancies or lymphoma that has spread to other places in the body or cannot be removed by surgery. Trigriluzole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab and pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving trigriluzole in combination with nivolumab and pembrolizumab may work better at treating patients with solid malignancies or lymphoma.

PRIMARY OBJECTIVES:

I. The primary objective of this study is to determine the safety of trigriluzole in combination with PD-1 inhibiting antibodies, and to define a maximum tolerated dose (MTD) of trigriluzole in combination therapy.

SECONDARY OBJECTIVES:

I. To characterize the efficacy of the combination therapy. II. To identify markers of response to trigriluzole in the tumor microenvironment.

OUTLINE: This is a dose-escalation study of trigriluzole.

Patients receive trigriluzole orally (PO) every other day (QOD), twice daily (BID), every morning (QAM) or every bedtime (QHS) on days -14 to -1. Patients then receive nivolumab intravenously (IV) over 60 minutes every 2 weeks beginning week 1 and trigriluzole PO QOD, BID, QAM or QHS. Once the MTD of trigriluzole with nivolumab is identified, patients receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for up to 3 years.

Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

A Phase I Study to Evaluate the Safety of Trigriluzole (FC-4157/BHV-4157) in Combination With PD-1 Blocking Antibodies

The MTD of trigriluzole in combination with nivolumab will be identified. The MTD will then be tested in combination with pembrolizumab using the same escalate/de-escalate/stay rules. Data on the adverse event type, severity and frequency will be recorded.

A DLT was any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) that was possibly Trigriluzole or Nivolumab related. CTCAE 3.0 Grade 3 is a severe AE and Grade 4 is a life- threatening or disabling AE. DLTs were collected to determine the Maximum-Tolerated Dose (MTD), which is defined as the dose level below the dose at which 33% of participants experienced a DLT.

Continuous variables will be presented by summary statistics (such as mean, median, standard error and 95% confidence intervals \[CI\]) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 95% CI).

Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

National Cancer Institute (NCI)

Rutgers, The State University of New Jersey

Assistant Professor, Medical Oncology

Cohort 1: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV), for 2 weeks, and Trigriluzole 140 mg (PO), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 140 mg Taken by Mouth Daily (PO)

Cohort 2: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV), for 2 weeks, and Trigriluzole 140 mg (PO) Twice a day (BID), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 140 mg PO Twice a Day (BID)

Cohort 3: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV) and Trigriluzole 140 mg (PO) once a day in the morning (QAM) and 280mg PO every night at bedtime (QHS), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 140 mg /280mg

Cohort 4: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV) and Trigriluzole 140 mg (PO) once a day in the morning (QAM) and 280mg PO every night at bedtime (QHS), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole 200mg PO BID. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 280mg PO BID

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Dr. Biren Saraiya - Associate Professor of Medicine Medical Director, Office of Human Research Servi

All participants who received at least 1 dose of Trigriluzole (140 mg or 280mg ) in combination with Nivolumab (240mg IV)

All Participants

Maximum Tolerated Dose (MTD))/Recommended Phase 2 Dose of Trigriluzole

Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)

Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 280mg PO BID

Objective Response Rate Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1

Overall Survival

Time to Next Therapy or Death

Freedom From New Metastases

Landmark Survival Rates at 1 Year

Landmark Survival Rate at 2 Years

Duration of Response for Responding Patients

Progression Free Survival

Time to Treatment Failure

Overall Study

Patients without cancer undergo collection of blood and urine samples for analysis via MDSC clinical assay at baseline, 1 week, and 4 months.

Patients with localized bladder cancer undergo collection of blood and urine samples for analysis via MDSC clinical assay at baseline, 1 week, and within 4 weeks after cystectomy.

Patients with metastatic cancer undergo collection of blood and urine samples for analysis via MDSC clinical assay at baseline, 1 week, and within 4 weeks after completion of 4 courses of systemic chemotherapy.

Undergo collection of blood and urine samples

Cytology Specimen Collection Procedure

Jacek Pinski

This pilot research trial studies how well myeloid derived suppressor cells (MDSC) clinical assay works in finding and monitoring cancer cells in blood and urine samples from patients with or without localized or metastatic bladder cancer. Studying samples of blood and urine from patients with or without bladder cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer and may help doctors improve ways to diagnose and treat patients.

PRIMARY OBJECTIVES:

I. To evaluate a novel clinical assay (MDSC clinical assay) to detect cancer associated immune cells in the peripheral blood of patients as a means to better detect and monitor malignant bladder cancer in patients.

II. Estimate mean MDSC level, intra-patient variability, and inter-patient variability, for 3 groups of subjects with variable bladder cancer disease status at baseline.

III. In patients with known localized, muscle-invasive bladder cancer who undergo surgical treatment: to determine the change in MDSC level from baseline to after treatment including surgery.

IV. In patients with known metastatic bladder cancer who undergo systemic treatment: to determine the change in MDSC level from baseline to after 4 cycles of treatment compared to the change in tumor burden as evaluated by radiographic imaging.

V. In patients with no history of cancer: to determine the changes in MDSC levels from baseline to after 4 months.

SECONDARY OBJECTIVES:

I. Compare MDSC level measurements to urine cytology analysis at baseline and after treatment to determine whether the two tests correlate in any of the 3 groups of patients defined in this study.

OUTLINE:

GROUP I: Patients without cancer undergo collection of blood and urine samples for analysis via MDSC clinical assay at baseline, 1 week, and 4 months.

GROUP II: Patients with localized bladder cancer undergo collection of blood and urine samples for analysis via MDSC clinical assay at baseline, 1 week, and within 4 weeks after cystectomy.

GROUP III: Patients with metastatic cancer undergo collection of blood and urine samples for analysis via MDSC clinical assay at baseline, 1 week, and within 4 weeks after completion of 4 courses of systemic chemotherapy.

MDSC Clinical Assay in Finding and Monitoring Cancer Cells in Blood and Urine Samples From Patients With or Without Localized or Metastatic Bladder Cancer

MDSC Clinical Assay for Cancer Detection and Monitoring in Bladder Carcinoma

The direction and magnitude of the changes in Group 3 will be compared to the changes in tumor burden assessed radiographically - to explore the associations.

The MDSC levels at baseline will be compared (plots and correlations) to the urine cytology levels (Groups 2 and 3) to describe any associations; for Group 3, the changes (baseline to post treatment) in the MDSC levels will be compared to the changes in urine cytology.

University of Southern California

Gland and Hormone Related Diseases

Uterine Cervical Neoplasms

Breast Neoplasms

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Neoplasms

Endometrial Neoplasms

Breast Diseases

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Uterine Cervical Diseases

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Anti-Infective Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Patients receive nanoparticle albumin-bound rapamycin IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

Nanoparticle Albumin-Bound Rapamycin

Quality-of-Life Assessment

Mitesh Borad

This pilot trial studies how well nanoparticle albumin-bound rapamycin works in treating patients with cancer that as has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced cancer) and that has an abnormality in a protein called mechanistic target of rapamycin (mTOR). Patients with this mutation are identified by genetic testing. Patients then receive nanoparticle albumin-bound rapamycin, which may stop the growth of cancer cells by blocking the mTOR enzyme, which is needed for cell growth and multiplication. Using treatments that target a patient's specific mutation may be a more effective treatment than the standard of care treatment.

PRIMARY OBJECTIVES:

I. To investigate efficacy of groups of patients defined by disease type, genomic aberration and treatment regimen.

II. To assess the confirmed response rate of nanoparticle albumin-bound rapamycin (nab-rapamycin) in mTOR aberrant advanced cancers. (Sub-protocol Arm A)

SECONDARY OBJECTIVES:

I. To estimate other clinical outcomes (e.g., progression-free and overall survival) of groups of patients defined by disease type, genomic aberration and treatment regimen.

II. To describe the adverse event profile of each regimen. III. To assess the clinical benefit rate of nab-rapamycin in mTOR aberrant advanced cancers. (Sub-protocol Arm A).

IV. To estimate progression-free survival (specifically at 6 months) and overall survival of these patients. (Sub-protocol Arm A) V. To estimate the adverse event profile of nab-rapamycin. (Sub-protocol Arm A)

TERTIARY OBJECTIVES:

I. To describe patient health-related quality of life (HRQOL) and symptoms using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C)30 in groups of patients defined by disease type and/or treatment regimen and to correlative HRQOL/symptoms with genomic markers.

II. To assess the rate of individual mTOR pathway aberrations and assess the association between individual mTOR pathway aberrations and clinical outcome both across disease indications and within disease indications. (Sub-protocol Arm A)

OUTLINE:

Patients receive nanoparticle albumin-bound rapamycin intravenously (IV) over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

A Pilot Study of a Rapid Access Platform for Investigational Drugs (RAPID) in Advanced Cancers

Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall and by disease group where warranted by sample size. Changes from baseline at each cycle will be statistically tested using paired t-tests, and standardized response means (mean of the change from baseline scores at a given cycle, divided by the standard deviation of the change scores) will be interpreted (after applying Middel's adjustment) using Cohen's cut-offs.

Will be described, and association with confirmed response will be investigated using a Fisher's exact test. Associations with time to progression and overall survival will be investigated using log-rank tests. Analysis will be carried out overall and within disease groups where warranted by sample size.

The proportion of confirmed responses will be estimated by the number of confirmed responses divided by the total number of evaluable patients. An exact binomial confidence interval for the true confirmed response proportion will be calculated. Analysis will be carried out overall and within disease groups where warranted by sample size.

An exact binomial confidence interval for the true confirmed clinical benefit rate will be calculated. Analysis will be carried out overall and within disease groups where warranted by sample size.

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Analysis will be carried out overall and within disease groups where warranted by sample size.

The distribution of survival time will be estimated using the method of Kaplan-Meier. Analysis will be carried out overall and within disease groups where warranted by sample size.

The distribution of time to progression will be estimated using the method of Kaplan-Meier. The 6-month progression-free rate will be provided. Analysis will be carried out overall and within disease groups where warranted by sample size.

Mayo Clinic

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma	NCT03229278	Lymphoma Metastatic Mali... Metastatic Mela... Metastatic Rena... Recurrent Bladd... Recurrent Class... Recurrent Head ... Recurrent Lymph... Recurrent Malig... Recurrent Renal... Stage III Bladd... Stage III Lymph... Stage III Non-S... Stage III Renal... Stage III Skin ... Stage IIIA Non-... Stage IIIA Skin... Stage IIIB Non-... Stage IIIB Skin... Stage IIIC Skin... Stage IV Bladde... Stage IV Lympho... Stage IV Non-Sm... Stage IV Renal ... Stage IV Skin M... Stage IVA Bladd... Stage IVB Bladd... Unresectable He... Unresectable So...	Enzyme Inhibito... Laboratory Biom... Nivolumab Pembrolizumab	18 Years -	Rutgers, The State University of New Jersey
MDSC Clinical Assay in Finding and Monitoring Cancer Cells in Blood and Urine Samples From Patients With or Without Localized or Metastatic Bladder Cancer	NCT02735512	No Evidence of ... Stage II Bladde... Stage III Bladd... Stage IVA Bladd... Stage IVB Bladd...	Cytology Specim... Laboratory Biom...	-	University of Southern California
Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations	NCT02646319	Advanced Malign... Cervical Squamo... Endometrial Car... Malignant Uteri... Recurrent Bladd... Recurrent Breas... Recurrent Cervi... Recurrent Head ... Recurrent Malig... Recurrent Ovari... Recurrent Prost... Recurrent Renal... Solid Neoplasm Stage III Bladd... Stage III Prost... Stage III Renal... Stage IIIA Brea... Stage IIIA Cerv... Stage IIIA Ovar... Stage IIIB Brea... Stage IIIB Cerv... Stage IIIB Ovar... Stage IIIC Brea... Stage IIIC Ovar... Stage IV Breast... Stage IV Ovaria... Stage IV Prosta... Stage IV Renal ... Stage IVA Bladd... Stage IVA Cervi... Stage IVB Bladd... Stage IVB Cervi...	Laboratory Biom... Nanoparticle Al... Quality-of-Life...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for stage ivb bladder cancer