Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Heart Failure

Cardiotoxicity

Breast Diseases

Skin Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Micronutrients

All Drugs and Chemicals

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Niacinamide

Niacin

Nicotinic Acids

Folic Acid

Vitamin B Complex

Trace Elements

Hypolipidemic Agents

Antimetabolites

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

The patients randomised into this arm of the trial will receive 500 mg Nicotinamide Riboside b.i.d. The duration of blinded therapy will depend on the duration of anthracycline therapy, and will for some patients last for 3 months, others for 6 months.

The patients randomised into this arm of the trial will receive a matching placebo b.i.d. The duration of treatment is equivalent to the description in the treatment arm.

Nicotinamide Riboside 500mg b.i.d as long as the patient is receiving anthracycline therapy

Nicotinamide Riboside

Matching placebo b.i.d as long as the patient is receiving anthracycline therapy

Placebo

Torbjørn Omland, MD, PhD

Victoria Vinje, MD

Jürgen Geisler, MD, PhD

Evandro F Fang, PhD

Breast cancer is the most common form of cancer in women. Modern breast cancer treatments have led to increased survival, but at the same time, increased risk for cardiotoxicity and development of heart failure. In this study, the investigators want to evaluate whether nicotinamide riboside can prevent cancer-related cardiac dysfunction in metastatic breast cancer patients scheduled for anthracycline therapy. Further, the investigators will evaluate change in signs of skeletal muscle injury and functional capacity.

The trial is prospective, randomised, double-blind and placebo-controlled. The primary objective is change in left ventricular ejection fraction (LVEF), determined by cardiac MRI (CMR). Secondary objectives are change in circulating high-sensitivity cardiac troponin I and T (hs-TnI and hs-TnT), Creatine Kinase (CK) and myoglobin, and various measurements of change in left ventricular systolic function determined by CMR and echocardiography. Additional assessments are evaluation of the patient's functional capacity and the patients will be asked to fill out questionnaires to assess quality of life.

60 patients will be randomised in a 1:1 ratio. The duration of blinded therapy will depend on the duration of anthracycline therapy. All patients will be examined at baseline and 3 months, and if the patient is scheduled for extended anthracycline therapy, an additional examination will be performed at 6 months.

Double-blind, randomised, placebo-controlled

The IMP and matching placebos will be provided by the manufacturers of ChromaDex. The Data Safety Committee will have the treatment allocation list.

Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients

Effect of Nicotinamide Riboside on Myocardial and Skeletal Muscle Injury and Function in Patients With Metastatic Breast Cancer Receiving Anthracyclines

Changes in the amount of circulating NAD+ will be measured using commercial kits and Liquid chromatography-mass spectrometry analyses (LC-MS analyses)

Change in transverse relaxation time (T2) measured by CMR

Change in longitudinal relaxation time (T1) measured by CMR

Change in left ventricular diastolic function as measured by echocardiography

Change in the aortic pulse wave velocity measured by CMR

Chance in circulating N-terminal pro b-type natriuretic peptide (NT-proBNP)

Chance in circulating cardiac myosin binding protein C (cMyC)

Change in circulating creatine kinase (CK)

Quality of life measured by Chalder Fatigue Scale. Items are rated on a 4-point Likert scale (0 = better than usual, 1 = no more than usual, 2 = worse than usual, 3 = much worse than usual), with higher scores indicating greater fatigue.

Quality of life measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Range in score from 0 to 100. A high scale score represents a higher response level.

Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / Quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Quality of life measured by European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L). Each dimension in the EQ-5D-5L has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). There are 3,125 possible health states defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health).

Change in left ventricular ejection fraction (LVEF), as determined by CMR from randomization to end of blinded therapy.

From randomization to the end of blinded therapy:

Change in LVEF, as determined by echocardiography

From randomization to the end of blinded therapy:

Change in left ventricular global longitudinal strain (GLS), as determined by echocardiography

From randomization to the end of blinded therapy:

Change in left ventricular global circumferential strain (GCS) and GLS, as determined by CMR

From randomization to the end of blinded therapy:

Change in left ventricular end-systolic volume measured by CMR

From randomization to the end of blinded therapy:

Change in circulating hs-cTnT

From randomization to the end of blinded therapy:

Change in circulating hs-cTnI

From randomization to the end of blinded therapy:

Change in distance in meters during 6-minute walk test

From randomization to the end of blinded therapy:

Change in force generated by handgrip strength test

ChromaDex, Inc.

Norwegian Cancer Society

Norwegian Breast Cancer Association

Helse Sor-Ost

University Hospital, Akershus

Professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Testicular Neoplasms

Endometrial Neoplasms

Endocrine Gland Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Genital Neoplasms, Male

Genital Diseases, Male

Male Urogenital Diseases

Testicular Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Anticonvulsants

Antibodies

Cannabidiol

Immunoglobulins

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the IL7/CCL19 secreting CAR-NK cell therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus CBD therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus NAD therapy group.

Engineering Claudin6, GPC3, Mesothelin, or AXL targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Lag3 secreting vector into NK cells, which are isolated from patients with advanced ovarian cancer or other cancers with expression of Claudin6, GPC3, Mesothelin, or AXL, and then transfusing them back the patients.

In some cases, the CAR-NK cells will be combined with CBD or NAD to enhance the therapeutic efficacy.

Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

Zhenfeng Zhang, MD, PHD

Bingjia He, MD

This study is an open, exploratory clinical study to evaluate the safety and preliminary efficacy of Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in patients with Claudin6, GPC3, Mesothelin, or AXL-positive advanced solid tumors (ovarian cancer and others)

1. Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study;
2. Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6, GPC3, Mesothelin, or AXL targeting CAR, amplify the number of transfected NK cells as needed, test the quality and killing activity of the Claudin6, GPC3, Mesothelin, or AXL-CAR-NK cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
3. To enhance the killing capability, some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3; some CAR-NK cells are combined with Cannabidiol(CBD) or Nicotinamide adenine dinucleotide (NAD);
4. Evaluate the clinical results as needed.
5. Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.

CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors

Phase I Trial to Evaluate Safety and Preliminary Efficacy of CLDN6/GPC3/Mesothelin/AXL-CAR-NK in Patients With CLDN6/GPC3/Mesothelin/AXL-positive Advanced Solid Tumors

The type, frequency, severity, and duration of adverse events as a result of Claudin6, GPC3, Mesothelin, or AXL- CAR-NK cells infusion will be summarized.

Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response, prior to progression or further anti-cancer therapy.

Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after the first dose) is observed as best overall response.

Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1/recurrence) or death from any cause, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients	NCT05732051	Breast Cancer Metastatic Brea... Cancer Therapy-... Cardiotoxicity Heart Failure	Nicotinamide Ri... Placebo	18 Years -	University Hospital, Akershus
CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors	NCT05410717	Stage IV Ovaria... Testis Cancer, ... Endometrial Can... CAR NK	Claudin6, GPC3,...	18 Years - 75 Years	Second Affiliated Hospital of Guangzhou Medical University

Spots Global Cancer Trial Database for nicotinamide adenine dinucleotide