Efficacy and Safety of MitoQ in Improving Cancer Cachexia

Primary Efficacy Endpoint:

To evaluate the preliminary efficacy of MitoQ in patients with cancer cachexia by comparing muscle function before and after MitoQ administration at Weeks 7 and 13, as assessed by handgrip strength and the 6-minute walk test (6MWT).

Key Secondary Efficacy Endpoints:

Inflammatory and Metabolic Markers: Changes in the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α); effects on oxidative stress markers (MDA, SOD, GPx); and levels of prealbumin and serum albumin.

Clinical Benefit Endpoints:

Changes in skeletal muscle mass at Weeks 7 and 13, as measured by the skeletal muscle index (SMI) at the third lumbar vertebra (L3) level using computed tomography (CT), as well as changes in body weight, including total body weight, fat mass, and lean body mass.

Quality of life and symptom assessment using validated instruments: the EORTC QLQ-C30 (quality of life), the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), the Hospital Anxiety and Depression Scale (HADS), and the Cancer Fatigue Scale (CFS).

Other Secondary Efficacy Endpoints:

Tumor Response and Survival Endpoints: Objective response rate (ORR) based on RECIST version 1.1 criteria and progression-free survival (PFS).

Safety Assessment: Hepatic function tests and lipid profile. Exploratory Endpoints: Exploratory biomarkers including metabolic and inflammatory factors.

Safety Endpoints:

Vital signs, physical examination, laboratory parameters, electrocardiogram (ECG), echocardiography, and adverse events (AEs), with AEs graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Inclusion criteria

• Subjects must meet all of the following inclusion criteria at screening to be eligible for enrollment in this study:

Subjects aged ≥ 18 years at the time of screening. Subjects who are willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures.

Ability to sign the informed consent form. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy of more than 3 months. Patients with histologically or cytologically confirmed malignant solid tumors (patients with hepatocellular carcinoma may be enrolled based on clinical diagnosis).

Medically documented cachexia or pre-cachexia (patient-reported weight loss data are acceptable for patients receiving first-line treatment):

Cachexia: Involuntary weight loss of >5% within 6 months prior to screening. Pre-cachexia: Involuntary weight loss of ≤5% within 6 months prior to screening, accompanied by anorexia or metabolic alterations.

Adequate organ function, as defined by the following:

Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless the subject has a confirmed diagnosis of Gilbert's syndrome.

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; if tumor involves the liver, ≤ 5.0 × ULN.

Creatinine ≤ 2 mg/dL, or glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m², calculated according to the Modification of Diet in Renal Disease (MDRD) formula.

Subjects of childbearing potential must agree to use at least one medically acceptable and effective method of contraception during sexual intercourse throughout the study period and for 6 months after the last dose of study drug, and must have no plans for pregnancy or sperm/egg donation.

Subjects who clearly understand the study, voluntarily agree to participate, and sign the informed consent form personally.

Exclusion criteria

• Subjects presenting with any of the following at screening will not be eligible for enrollment in this study:

Known hypersensitivity to MitoQ capsules or any of the excipients. Subjects with known symptomatic brain metastases requiring regular use of corticosteroids. Asymptomatic or previously diagnosed brain metastases may be included if the following conditions are met: treatment has been completed, and the subject has recovered from acute effects of radiation therapy or surgery prior to screening; corticosteroid therapy for brain metastases has been discontinued, and the neurological status is stable prior to the first dose of study drug.

Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (subjects with HBV-DNA < 10⁴ IU/mL may be enrolled).

Known positive test for human immunodeficiency virus (HIV) or positive treponemal antibody (TP-Ab) test.

Currently existing reversible reduction in food intake, as determined by the investigator, including but not limited to:

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 oral mucositis; NCI CTCAE Grade 3 or 4 gastrointestinal (GI) disorders (e.g., nausea, vomiting, diarrhea, and constipation); Mechanical obstruction preventing oral intake. Receiving tube feeding or parenteral nutrition (whether total or partial parenteral nutrition) at the time of screening.

Major surgery within 4 weeks prior to the first dose of study drug (central venous access device placement and tumor biopsy are not considered major surgery); subjects must have adequately recovered from the acute effects of surgery prior to screening, and no major surgery should be planned during the study period.

Severe gastrointestinal disorders (including esophagitis, gastritis, and malabsorption).

History of subtotal gastrectomy or small bowel resection (more than one-third).

Cachexia caused by other conditions, as determined by the investigator, including but not limited to:

Severe chronic obstructive pulmonary disease (COPD); New York Heart Association (NYHA) Class III or IV heart failure; Acquired immunodeficiency syndrome (AIDS). Any of the following events within the past 3 months: myocardial infarction, congenital long QT syndrome, torsades de pointes, cardiac arrhythmia (including sustained ventricular tachycardia and ventricular fibrillation), unstable angina, coronary artery or peripheral artery bypass graft, symptomatic congestive heart failure (CHF, NYHA Class III or IV), severe cerebrovascular accident, or symptomatic pulmonary embolism or other clinically significant cardiovascular/thromboembolic disease.

Persistent malignant arrhythmia of NCI CTCAE Grade ≥ 2. Initiation of new systemic corticosteroid therapy within 4 weeks prior to the first dose of study drug. Stable corticosteroid therapy (i.e., no significant change in dose or frequency of administration within 4 weeks prior to the first dose) is permitted, such as dexamethasone used as a premedication or daily oral prednisone.

Planned anti-tumor therapy during the study that includes agents known to cause weight gain, such as ALK inhibitors, ROS1 inhibitors, or docetaxel, within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug.

Use of any prescription medication that increases appetite or ameliorates weight loss within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug, including but not limited to anamorelin, medroxyprogesterone acetate, dronabinol, medical cannabis, etc.

Currently receiving another investigational drug, or use of another investigational drug within 4 weeks prior to the first dose of study drug or within 5 half-lives of the previous investigational drug (whichever is longer).

Female subjects who are pregnant or breastfeeding. Any other acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk associated with study participation or use of the study drug, or that may interfere with the interpretation of study results. The investigator may exclude a subject from participation if, in the investigator's judgment, the subject is unsuitable for enrollment in this study for any of these reasons.