Clinical Trial Protocol: Randomized Placebo-Controlled Pilot Study of GcMAF (Soloways TM) in Patients With Metastatic Breast Cancer

This randomized, double-blind, placebo-controlled pilot study aims to evaluate the efficacy and safety of GcMAF (Gc Macrophage Activating Factor) in female patients with metastatic breast cancer. The primary objective is to assess the reduction in serum nagalase levels, an enzyme associated with tumor activity, over a six-month period, and to evaluate improvements in clinical outcomes. The study involves 60 patients who will be divided into two groups: one receiving weekly injections of GcMAF and the other receiving a placebo.

Patients eligible for the study must have histologically or cytologically confirmed metastatic breast cancer, completed at least one line of systemic therapy, and have elevated serum nagalase levels. Additional inclusion criteria include female patients aged 18 to 70 years, ECOG performance status of 0 to 2, adequate bone marrow, liver, and renal function, and an estimated life expectancy of at least six months. Patients must also agree to use effective contraception and provide informed consent.

The primary endpoint is the change in serum nagalase levels from baseline to six months. Measurements will be taken at baseline, monthly, and at the end of the study using standardized enzymatic assays. Secondary endpoints include clinical status, assessed through objective tumor response using RECIST criteria and performance status using the ECOG scale, quality of life evaluated through EORTC QLQ-C30 questionnaires, immune activity measured by flow cytometry for various immune cell subsets, and inflammation markers such as CRP, interleukins, and TNF-alpha measured by ELISA. Adverse effects will be monitored weekly and categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

The study procedures include initial screening to measure baseline nagalase levels and assess eligibility, followed by randomization into the GcMAF or placebo groups. Patients will receive weekly injections for six months, with monthly assessments of nagalase levels, clinical status, quality of life, and blood samples for immune and inflammation markers. Interim assessments will occur at three months, with final assessments and data analysis at six months.

Exclusion criteria

include the presence of other active malignancies, severe uncontrolled illnesses, pregnancy or breastfeeding, previous treatment with GcMAF, and known hypersensitivity to the study drug components. The study timeline consists of patient recruitment and baseline measurements in the first month, followed by six months of treatment and monitoring, with interim and final assessments and subsequent data analysis.

This study aims to determine if GcMAF can significantly reduce serum nagalase levels and improve clinical outcomes, including tumor response, performance status, quality of life, and immune and inflammation markers, in patients with metastatic breast cancer. The results will provide insight into the potential therapeutic benefits of GcMAF for this patient population.

Inclusion criteria

• Diagnosis:

• Histologically or cytologically confirmed metastatic breast cancer.
• Evidence of metastatic disease, confirmed by imaging studies (CT, MRI, or PET scans) and/or biopsy. 2. Prior Treatment:
• Patients must have completed at least one line of systemic therapy (e.g., chemotherapy, hormone therapy, targeted therapy) for metastatic breast cancer.
• A minimum of 4 weeks must have elapsed since the last chemotherapy, targeted therapy, or radiotherapy before starting the study treatment. 3. Age:
• Female patients aged 18 to 70 years. 4. Performance Status:
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 5. Life Expectancy:
• Estimated life expectancy of at least 6 months. 6. Laboratory Values:
• Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/L, and hemoglobin ≥ 9 g/dL.
• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases).
• Adequate renal function: Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m^2 (calculated using the Cockcroft-Gault formula). 7. Contraception:
• Women of childbearing potential must agree to use effective contraception (e.g., hormonal contraceptives, intrauterine device, barrier methods, or abstinence) during the study and for at least 6 months after the last dose of study treatment. 8. Informed Consent:
• Ability to understand and willingness to sign a written informed consent document.

• Compliance:
• Willingness and ability to comply with the study protocol, including scheduled visits, treatment plans, laboratory tests, and other study procedures. 10. Nagalase Levels: • Elevated serum nagalase levels above the normal range, indicating active tumor burden.

Exclusion criteria

• Concurrent Malignancies:

• Presence of other active malignancies (excluding adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix). 2. Severe Comorbid Conditions:
• Severe uncontrolled concurrent illness, such as significant cardiovascular disease (e.g., uncontrolled hypertension, recent myocardial infarction), severe pulmonary conditions (e.g., uncontrolled asthma, chronic obstructive pulmonary disease), or active infections requiring systemic therapy. 3. Pregnancy and Lactation:
• Pregnant or breastfeeding women. 4. Previous GcMAF Treatment:
• Previous treatment with GcMAF. 5. Allergies and Sensitivities:
• Known hypersensitivity to any component of the study drug or its formulation.