Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Melanoma

Sarcoma

Lymphoma

Endocrine Gland Neoplasms

Endocrine System Diseases

Soft Tissue Sarcoma

Lymphosarcoma

Psychotropic Drugs

All Drugs and Chemicals

Psilocybin

Hallucinogens

Single high-dose (25mg) capsule of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy

Sarah Hales, MD

Emma Hapke, MD

Daniel Rosenbaum, MD

The PEARL Pilot is a phase II open-label trial. Participants will receive a single high-dose (25 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

Individuals with advanced cancer often experience high levels of distress due to physical suffering, difficult treatment decisions, social isolation, and fear of death. While there are many treatment options for the management of physical symptoms associated with cancer, there are relatively few standard treatment approaches to help patients deal with psychological and existential suffering. Over the past decade, research has shown that psychotherapies incorporating existential, attachment and relational approaches can address the specific needs and challenges of the advanced cancer population and thus help to reduce distress. Simultaneously, recent research has shown that psilocybin-assisted psychotherapy, in which, an individual ingests the psychoactive drug within the carefully monitored therapeutic setting, can reduce end-of-life distress and greatly benefit those with advanced disease. The multidisciplinary team has combined these two evidence-based approaches into what the team calls Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose drug session, and integration sessions, with important elements from manualized individual psychotherapies designed for patients with advanced cancer. This study will assess the feasibility, acceptability, and safety of PEARL therapy among patients with advanced cancer. This study will yield important information about the feasibility of this type of therapy and contribute to the growing research around the efficacy of psychedelic-assisted therapies. This type of therapy has the potential to improve quality of life among those with advanced disease and careful research is needed to build upon previous findings to outline the necessary components of therapy and guide public policy, legislation, and clinical guidelines.

Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer

Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Phase II Open-Label Trial

Used to assess feasibility of PEARL therapy.

Participants will be interviewed regarding their experiences with PEARL, including acceptability and perceived positive and negative effects of the intervention, with a semi-structured interview guide.

Safety will be assessed throughout the trial. Adverse events (AEs) attributed to psilocybin will be monitored for and recorded after the psilocybin session. This study will use CTCAE v5.0 to assess AEs.

Serious adverse events (SAEs) will be tracked until study completion and will be defined as any adverse drug experience that: results in death; that is life-threatening (i.e. any AE that places the participant, in the view of the investigators, at immediate risk of death from the reaction as it occurs); requires hospital admission; results in persistent or significant disability (i.e. a substantial disruption of a person's ability to conduct normal life functions); or may jeopardize the participant or necessitate medical intervention to prevent one of the aforementioned criteria.

The Death and Dying Distress Scale (DADDS) is a 15-item self-report measure designed for populations facing imminent death and addresses fears about the dying process, and about lost opportunities and self-perceived burden placed on others as a result of impending mortality. Total score range is 0 to 75. Higher scores indicate greater death-related distress.

The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report scale measuring depressive symptoms. Total score range is 0 to 27. Higher scores indicate greater severity of depression.

The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item self-report scale used to screen for and measure anxiety symptoms. Total score range is 0 to 21. Higher scores indicate higher levels of anxiety.

The Demoralization Symptoms (DS) is a 24-item self-report measure that assesses loss of meaning and purpose, disheartenment, and helplessness. Total score range is 0 to 96. Higher scores indicate higher levels of demoralization.

The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) is a 12-item scale designed to measure important aspects of spirituality including sense of meaning in one's life, harmony, peacefulness and a sense of comfort and strength from one's faith. Total score range is 0 to 48. Higher scores indicate higher spiritual well-being.

The Quality of Life at the End of Life-Cancer (QUAL-EC) is a 17-item measure that includes subscales which assess symptom impact, preparation for end of life (i.e., the extent to which the family is prepared and financial plans have been made), relationship with healthcare providers (i.e., the extent to which patients feel informed and are able to participate in decisions about their care) and sense of life completion (i.e., being able to share important things and feel connected to others). For Symptom Control, score range is 3 to 15, with higher scores reflecting greater symptom control; for the Relationship with Healthcare Provider, score range is 5 to 25, with higher scores reflecting a better relationship with healthcare providers; for the Preparation for End-of-Life, score range is 4 to 20, with higher scores reflecting greater preparation for end-of-life; and the for Life Completion, score range is 5 to 25, with higher scores reflecting a greater sense of life completion.

The Schedule of Attitudes Toward Hastened Death (SAHD) is a 20-item self-report measure of desire for death in the medically ill. Total score range is 0 to 20. Higher scores indicate greater desire for death.

University Health Network, Toronto

Breast Neoplasms

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Breast Diseases

Skin Diseases

Lipid Regulating Agents

Atorvastatin

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Enzyme Inhibitors

One 40 mg Atorvastatin tablet each morning by mouth for 24 months

One placebo tablet each morning by mouth for 24 months.

40 mg tablet taken by mouth each morning for 24 months.

One placebo tablet taken each morning orally for 24 months.

Placebo

Gregory Hundley, MD

The purpose of this research study is to see if Atorvastatin (Lipitor) 40 mg by mouth daily decreases the chance of developing heart problems in individuals receiving adjuvant anthracycline-based chemotherapy for breast cancer of lymphoma.

PRIMARY OBJECTIVES:

Specific Aim 1:

To determine if Atorvastatin(Lipitor) administration preserves left ventricular ejection fraction (LVEF) 24 months after initiation of Anthracycline-based adjuvant therapy for adjuvant treatment of breast cancer or lymphoma.

Specific Aim 2:

To determine if baseline to 6-month differences in LVEF predict baseline to 24-month differences in LVEF after Anthracycline-based adjuvant therapy and concomitant atorvastatin therapy.

To achieve these aims, we will perform a double-blind, placebo-controlled, randomized clinical trial of 0 or 40 mg of atorvastatin/day in 278 individuals scheduled to receive Anthracycline-based chemotherapy for treatment of Stage I-III breast cancer or lymphoma Stage I-IV with a projected \> 2 year life expectancy. We will use innovative noninvasive magnetic resonance imaging (MRI) procedures to accurately measure LVEF. In addition, we will measure left ventricle (LV) volumes, myocardial strain, fibrosis, aortic pulse wave velocity (PWV) and wall thickness, all factors that can influence LVEF by altering LV pre-load, after-load, and contractility.19,20 Advanced serum biomarkers will be measured that assess for the presence of oxidative/nitrosative stress, systemic inflammation and circulating neurohormones that also may influence LVEF.

This study will test a new clinical paradigm to manage breast cancer: primary prevention of Anthracycline-based adjuvant therapy-related LV dysfunction using pre-treatment with low-cost statins. In addition, this trial will be the first systematic collection of data regarding the mechanism(s) and time course by which LV dysfunction and subsequent chronic heart failure (CHF) evolve in individuals given Anthracycline-based chemotherapy for breast cancer or lymphoma. These data will be useful to physicians trying to determine the optimal cardiac protection strategies when administering adjuvant chemotherapeutic regimens to their breast cancer or lymphoma patients. The objective of this research is to use inexpensive medications to preserve cardiovascular (CV) health and thereby improve overall survival in the growing number of breast cancer and lymphoma patients.

SECONDARY OBJECTIVES

Specific Aim 1:

To document the effect of Atorvastatin (Lipitor) on cognitive function using a battery of neurocognitive tests (HVLT, Rey-osterrieth Figure, controlled oral word association test (COWA), Trail-making Parts A and B, Digit Span and Grooved Pegboard) in breast cancer and lymphoma patients receiving an anthracycline.

Specific Aim 2:

To document the effect of Atorvastatin(Lipitor) on self-reported quality of life using validated questionnaires (PROMIS including: General form, Cog Concerns, Cog Abilities, Fatigue, Pain intensity and interference, Sleep Disturbance, Physical Functioning and Social Functioning) in breast cancer and lymphoma patients receiving an anthracycline.

Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular ejection fraction by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

24 month estimated values of clinical measurements obtained from Cardiac MRI End Diastolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

24 month estimated values of clinical measurements obtained from Cardiac MRI End Systolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

24 month estimated values of clinical measurements obtained from Cardiac MRI Stroke Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular mass by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

24 month estimated values of clinical measurements obtained from Cardiac MRI pulse wave velocity by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

24 month estimated values Hopkins Verbal Learning test (HVLT) total recall by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. Ranges from 0 to 36 and higher numbers reflect better recall.

24 month estimated values Controlled Oral Word Association (COWA) by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. The COWA uses the three letter set of C, F, and L to assess phonemic fluency. Individuals are given 1 min to name as many words as possible beginning with one of the letters. The procedure is then repeated for the remaining two letters. Ranges from 0 to the total number of correct words that begin with one of the letters in the set. There is no ceiling of a maximum score. Higher numbers reflect better verbal fluency.

Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Applied Cognition - General Concerns - Short Form 4a . Scores range from 4-20 and then adjusted by t-scores ranging from 30.1-63.8. Higher scores reflect better cognition. Linear models include baseline assessment and group and multiple imputation was utilized.

Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Fatigue Short Form 41. Scores range from 4-20 and then adjusted by t-scores ranging from 33.7-75.8. Higher scores reflect worse fatigue. Linear models include baseline assessment and group and multiple imputation was utilized.

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

Wake Forest University Health Sciences

Serious Adverse Event reporting begins after the informed consent is signed. Serious Adverse Events occurring within 30 days of study completion must be reported via FDA Form 3500 (MedWatch).

One 40 mg Atorvastatin tablet each morning by mouth for 24 months

Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.

Arm 1 - Atorvastatin

One placebo tablet each morning by mouth for 24 months.

Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.

Placebo: One placebo tablet taken each morning orally for 24 months.

Arm 2 - Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Number of participants on Medicare. Insurance categories are check all that apply, participants could report more than 1 insurance type.

Medicare

Number of participants on Medicaid. Insurance categories are check all that apply, participants could report more than 1 insurance type.

Medicaid

Number of participants on private health insurance. Insurance categories are check all that apply, participants could report more than 1 insurance type.

Private Insurance

Number of participants reporting having no health insurance

No Health Insurance

Defined as lymphoma or breast cancer (those were the only two types eligible for this trial).

Cancer Type

Clinical staging is based on the results of tests done before surgery, which may include physical examinations, ultrasound, and MRI scans. Cancer stages range from 1-4. The higher the number, the larger the cancer tumor and the more it has spread to nearby tissues. Stage 4 has spread to distant parts of the body. Higher stages are associated with worse prognosis.

Cancer Stage

Marital Status

Self reported highest level of education.

Education

Income

Job Status

Body Mass Index

Lead Biostatistician

Linear models adjusting for baseline values and utilized multiple imputation for missing data.

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Left Ventricular Ejection Fraction (LVEF)

End Diastolic Volume

End Systolic Volume

Stroke Volume

Left Ventricular (LV) Mass

Pulse Wave Velocity

Those with data available at baseline and 24 months.

Hopkins Verbal Learning Test (HVLT) Total Recall

Controlled Oral Word Association (COWA)

Those with baseline and 24 month assessment completed. Multiple imputation was utilized for missing data.

Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Applied Cognition - General Concerns - Short Form 4a

Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Fatigue Short Form 41

Overall Study

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Carcinoma, Renal Cell

Lung Neoplasms

Urinary Bladder Neoplasms

Hodgkin Disease

Melanoma, Cutaneous Malignant

Squamous Cell Carcinoma of Head and Neck

Skin Neoplasms

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

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

Clear Cell Renal Cell Carcinoma

Hodgkin Lymphoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Nivolumab

Pembrolizumab

Antibodies

Immunoglobulins

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).

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

Age, Categorical

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)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer	NCT06416085	Advanced Cancer Stage IV Solid ... Stage IV Sarcom... Stage IV Lympho... Stage IV Melano... Endocrine Cance...	Psilocybin	18 Years -	University Health Network, Toronto
Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)	NCT01988571	Breast Cancer Lymphoma	Atorvastatin Placebo	21 Years - 100 Years	Wake Forest University Health Sciences
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

Spots Global Cancer Trial Database for stage iv lymphoma