Behaviors and Mental Disorders

All Conditions

Substance Related Disorders

Cognitive Dysfunction

Chemotherapy-Related Cognitive Impairment

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Herbal and Botanical

All Drugs and Chemicals

Ashwagandha

Placebo

Michele Guillen

Carol Parise, PhD

Deepti Behl, MD

This is a 1:1 randomized double blinded placebo controlled trial. • To determine if ashwagandha can improve cognitive dysfunction when compared with placebo in patients undergoing chemotherapy for cancer.

Patients are eligible if they are currently undergoing chemotherapy or treatment with chemotherapy in the past year and state that they notice thinking or memory problems. Patients will be given FACT-Cog PCI (Version 3). Patients that score less than 63, a score that reflects moderate to severe cognitive problems, are confirmed eligible. Subjects will be randomized 1:1 in blocks of 4.

Thyroid hormone testing will be conducted at baseline and at the end of week 6 for patients with a history of thyroid disease.

Patients will receive ashwagandha 350 mg po BID or placebo. The investigators and participants will be blinded to group assignment.

Endpoint testing including the FACT-Cog PCI and total score, Hopkins verbal learning test, trail making test (abstraction and executive function), and Mini Mental Status Exam (MMSE) will be administered at baseline and after 9 weeks of treatment. Six months after stopping the study, patients will receive a link to a REDCap database to complete the FACT-Cog and state whether they used ashwagandha once they completed the study.

Active study participation will be for 9 weeks.

This is a 1:1 randomized double blinded placebo controlled trial.

Ashwagandha for Cognitive Dysfunction

A Randomized Placebo-controlled Trial of Ashwagandha (Withania Somnifera) for Cognitive Dysfunction Associated With Cancer Chemotherapy.

The Functional Assessment of Cancer Therapy - Cognition (FACT-Cog) is a 37-item questionnaire designed to assess cognitive complaints in patients with cancer. The Perceived Cognitive Impairment (PCI) subscale consists of 20 items designed to measure perceived impairment in quality of life. Scores range from 0-72 where higher scores indicate less impairment and better quality of life.

Sutter Health

Principal Investigator

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Lung Diseases

Respiratory Tract Diseases

Thoracic Neoplasms

Respiratory Tract Neoplasms

Bronchial Neoplasms

Carcinoma, Bronchogenic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Quality of Life

Antineoplastic Agents

Osimertinib

Immunomodulating Agents

Afatinib

Erlotinib Hydrochloride

Gefitinib

Patients with EGFR mutation-positive locally advanced or metastatic NSCLC who have progressed while on or after receiving front-line EGFR-TKI therapy (e.g., gefitinib, erlotinib, afatinib, or icotinib).

Patients newly diagnosed with locally advanced or metastatic NSCLC who are treatment naive or patients who were diagnosed at an earlier stage but have progressed to metastatic NSCLC during the selection period.

HRQoL will be assessed using questionnaire EORTC QLQ-C30 and the questionnaire EORTC QLQ-LC 13.

These two questionnaires are validated instruments, translated in various languages and are not used as an intervention but rather to track patient quality of life and symptom reduction in real-life settings. Data for these patient reported outcomes will be collected prospectively from the time of enrolment until the end of follow-up. The two questionnaires will be self-administered by the patients in both cohorts at the enrolment visit and subsequently every 3 months (±1 month) at routine standard of care scheduled visits. The questionnaires are expected to take about 15 minutes to complete

Patient Reported Outcomes

Danielle Potter, PhD, MPH

This is an observational cohort study of patients with locally advanced or metastatic NSCLC (non-small cell lung cancer).

Patients will be recruited from participating sites in Europe, Asia, and Canada. The study will include 2 patient cohorts.

Study Design This will be an observational cohort study of patients with locally advanced or metastatic NSCLC (non-small cell lung cancer).

Patients will be recruited from participating sites in Europe, Asia, and Canada. Patients meeting the study inclusion/exclusion criteria will be selected during a 24-month enrolment period per country and will be followed from enrolment in the study until death, loss to follow-up, withdrawal of consent or study end date (whichever occurs earlier). Data Sources Data will be collected following enrolment in the study and entered in the electronic case report form (eCRF). All data will be collected using patient medical records. The investigator will be responsible for ensuring that all the required data is collected and entered into the eCRF. The site will collect the patient questionnaires and the data will be uploaded according to the data entry procedures.

Study Population

* Adult male or female patients (according to age of majority/adulthood as defined by local regulations) who have given written informed consent as per local regulations.
* The primary cohort will include patients with EGFR (epidermal growth factor receptor) mutation-positive locally advanced or metastatic NSCLC who have progressed while on or after receiving front-line EGFR-TKI (tyrosine kinase inhibitors) therapy (e.g., gefitinib, erlotinib, afatinib, or icotinib).
* Additionally, a secondary cohort of patients will include patients newly diagnosed with locally advanced or metastatic NSCLC who are treatment naive or patients who were diagnosed at an earlier stage but have progressed to metastatic NSCLC during the selection period.

Exposures There are no specific drug exposures or interventions being evaluated, as cohort eligibility (for both cohorts) is not exposure-based, but rather disease-based. All molecular testing and treatments will be at the discretion of the treating physician. Study Measures and Outcomes

* Patient demographic and clinical characteristics
* Molecular testing patterns and outcomes
* Treatment patterns
* Physician-reported clinical outcomes
* Cancer-related health care utilization
* Treatment- and biopsy-related complications
* CNS metastases (brain metastases and leptomeningeal metastases) and treatments associated with CNS (central nervous system) metastases
* HRQoL (Health Related Quality of Life) and symptoms Precision and Sample Size Estimations For the primary cohort the minimum sample size recommended for conducting a country-level analysis is 200 patients per country. This is based on the precision estimation calculation for the categorical study measure (% of patients tested) and will allow a maximum of

  * 8.3% precision (i.e., assuming 50% undergoing molecular testing) around the point estimate for the categorical measure. For the secondary cohort the minimum sample size recommended for conducting a country-level analysis is 300 patients which was determined using precision estimates calculated for a categorical (% of patients tested) and a time-to-event (overall survival) measure. The overall study will include approximately 2800-3300 patients across all participating countries across both primary (1200-1300 patients) and secondary (1600-2000 patients) cohorts. Statistical Analysis No formal hypothesis testing is specified. Study measures including patient demographics and clinical characteristics, molecular testing patterns, treatment sequence patterns, physician-reported outcomes (overall survival) and patient-reported outcomes (HRQoL) will be reported by primary and secondary cohorts, unless indicated otherwise. Continuous study measures (e.g., age, duration of therapy) will be reported descriptively with mean, standard deviation, median, minimum and maximum. Frequencies and percentages will be used to document categorical measures of interest (e.g., number and proportion of patients with a post progression molecular test, number and proportion of patients with a T790M mutation) and will include 95% CIs for key outcome variables. Kaplan-Meier curves and median survival will be estimated, overall and on an exploratory basis by clinical and treatment characteristics of interest (provided there are sufficient events available; e.g., chemotherapy vs. targeted therapy) as pre-specified in the statistical analysis plan.

Observational Study of Patients With Locally Advanced or Metastatic NSCLC (Non-Small Cell Lung Cancer)

Global PANORAMA Real World Molecular Testing, Treatment Patterns, and Clinical Outcomes in Patients With Locally Advanced or Metastatic NSCLC.

* Molecular testing rate defined as the number of patients identified as having received molecular testing divided by the number of patients in the cohorts
* Changes in testing rates over time (details will be included in the SAP)
* Molecular testing details including, but not limited to sample type, method of biopsy, testing turnaround time, test type, reason for testing, testing laboratory type, reason for not performing a test
* Molecular testing results including mutation status and type, test outcome, histologic/phenotypic transformation

* Overall survival measured from:

  * the date of initial diagnosis to date of death from any cause to the index date to date of death from any cause (for primary cohort only)
  * the date of first-line treatment until death
  * the date of second-line treatment until death
* Overall disease progression:

  o from date of treatment initiation until physician-reported progression, initiation of a new cancer-directed line of therapy (proxy for progression), or death
* For each line of chemotherapy/targeted therapy received:

  * Therapy regimen
  * Therapy duration measured as time from therapy start date to time of therapy end date
  * Number of cycles received
  * Reason for cessation of therapy
  * Time to initiation of new therapy defined as the time from start date of current therapy to start date of subsequent therapy
* For each surgery or radiotherapy received:

  * Type
  * Site
  * Date
* Any palliative/supportive care received

* For each health care setting:

  * Number and % of patients with visits
  * Total number of visits
* Total length of inpatient hospital and ICU stay

* For each treatment complication:

  o Rate of occurrence defined as the number of patients reporting at least one treatment-related complications divided by the number of evaluable patients2 Treatment-related complications can include, but are not limited to nausea and vomiting, diarrhoea, constipation, skin rash, infections, mouth sores, neutropenia, hyponatremia
* For each biopsy-related complication:

  * Rate of occurrence defined as the number of patients reporting at least one occurrence of the complication divided by the number of patients receiving a biopsy Biopsy-related complications can include but are not limited to collapsed lung, severe bleeding, bronchial spasms, irregular heart rhythms, death, severe chest pain, light-headedness, trouble breathing, excessive bleeding through the bandage, haemoptysis, fever, infection

Overall CNS metastases rate, defined as the number of patients developing CNS metastases divided by the number of evaluable patients

* Brain metastases rate, defined as the number of patients developing brain metastases divided by the number of evaluable patients
* Leptomeningeal metastases rate, defined as the number of patients developing leptomeningeal metastases divided by the number of evaluable patients
* Treatments for CNS metastases, including type of treatment and dates of treatment

• Change in score from baseline for each Quality of Life (QoL) domain and for overall QoL, measured at each subsequent site visit

AstraZeneca

Infections

Symptoms and General Pathology

Wounds and Injuries

Blood and Lymph Conditions

Rare Diseases

Communicable Diseases

Hyperthermia

Bacterial Infections

Neutropenia

Fever

Pseudomonas Infections

Gram-Positive Bacterial Infections

Disease Attributes

Body Temperature Changes

Agranulocytosis

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Mycoses

Bacterial Infections and Mycoses

Gram-Negative Bacterial Infections

Granulocytopenia

Anti-Infective Agents

Vancomycin

Cefepime

Ceftobiprole

Ceftobiprole medocaril

Anti-Bacterial Agents

Ceftobiprole Medocaril 500 mg every 8 hours 120-minute infusion \[250 mL\]

Cefepime with or without vancomycin 2 g every 8 hrs-30 min infusion vancomycin 1 000mg every 12 hrs-60 min infusion

Ceftobiprole Medocaril

Cefepime with or without vancomycin

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

The purpose of this study is to assess the safety and efficacy of ceftobiprole versus a comparator in patients with fever and neutropenia

This study is being discontinued due to issues regarding the comparator, cefepime. In Nov 2007 FDA issued a MedWatch regarding cefepime and the trial was suspended. As of May 14, 2008 the FDA was still evaluating the data on cefepime and final follow up is pending. There were no safety issues with ceftobiprole in this study based on the enrollment of 2 subjects in September of 2007. The study is being discontinued for administrative reasons. Ceftobiprole medocaril is a cephalosporin antibiotic with anti-MRSA (Methicillin-Resistant Staphylococcus Aureus) activity. Ceftobiprole is not yet approved, but undergoing regulatory review for treatment of skin infections. This is a randomized (patients are assigned to receive the different treatments under study based on chance), double-blind (neither the patient nor the physician knows whether the drug being investigated or the comparator agent is being taken), multicenter study of treatment with ceftobiprole medocaril versus treatment with a comparator in patients 18 years of age or older, who have fever and neutropenia after chemotherapy for cancer that requires intravenous therapy. Patients will be randomly assigned to receive either ceftobiprole medocaril or comparator. In addition, patients in the comparator group who are at risk of serious infections due to gram-positive pathogens (disease-causing bacteria) may also receive an antibiotic with MRSA activity. The study will consist of the following 3 phases: a prerandomization phase (includes screening and baseline assessments); a treatment phase, and a follow-up phase consisting of a primary efficacy visit and a late follow-up visit. The primary endpoint is the clinical cure rate. The total duration of of the study is determined by the time to resolution of fever and neutropenia and the conditions associated with the episode of fever and neutropenia. This is followed by the primary efficacy visit (7 to 10 days after the end of therapy) and the late follow-up visit (28 to 35 days after the end of treatment). Cultures (samples of blood or other suspected sites of infection) will be collected during the study as well as blood samples for hematology and chemistry (safety assessments). All adverse events will also be reported throughout the study and for about 4 to 5 weeks after the last dose of study drug. Patients will be randomized to either ceftobiprole or comparator for approximately 7 to 14 days.

A Study of Ceftobiprole in Patients With Fever and Neutropenia.

Multicenter, Randomized, Double-Blind Study of Ceftobiprole Versus Comparators in the Treatment of Patients With Fever and Neutropenia

Clinical cure rate (the ratio of the number of clinically cured patients to the total number of patients in the population) at 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter. Cure without modification: A subject will be considered to be cured at the primary efficacy visit if: The subject's fever and clinical signs and symptoms are resolved to the extent that no further anti-infective therapy is necessary as determined by the investigator Any infecting organisms that were identified at baseline were eradicated

To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the initial course of therapy, regardless of modification of therapy defined as addition of an anti-fungal agent and/or an aminoglycoside. Cure with modification: The subject requires antifungals, which will be considered a failure for the primary endpoint. The subject needs modification of study therapy by adding one or more agents (other than protocol-defined chemoprophylaxis antibiotics).

To compare the clinical success rate (absence or improvement of signs and symptoms of infection) at 72 hours after starting ceftobiprole with that of cefepime with or without vancomycin

To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the unmodified initial course of therapy, and receiving no prophylactic antibiotics after the EOT visit.

Basilea Pharmaceutica

500 mg every 8 hours - 120-minute infusion \[250 mL\]

2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion

Cefepime With or Without Vancomycin

Total

<=18 years

Between 18 and 65 years

>=65 years

Age Categorical

Female

Male

Gender

United States

Region of Enrollment

No analysis was performed due to early termination of the study.

Clincal Team Lead

No outcome measures were analyzed due to early termination of the study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ashwagandha for Cognitive Dysfunction	NCT04092647	Chemo Fog	Ashwagandha Placebo	18 Years -	Sutter Health
Observational Study of Patients With Locally Advanced or Metastatic NSCLC (Non-Small Cell Lung Cancer)	NCT03053297	Carcinoma, Non-...	Patient Reporte...	18 Years -	AstraZeneca
A Study of Ceftobiprole in Patients With Fever and Neutropenia.	NCT00529282	Fever Neutropenia Gram-positive B... Pseudomonas Inf...	Ceftobiprole Me... Cefepime with o...	18 Years -	Basilea Pharmaceutica

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