Business Decision

A randomized, double-blind, placebo-controlled, parallel study to evaluate the safety profile and ability of TW1025 oral solution to decrease fatigue in HER2-negative metastatic breast cancer patients receiving chemotherapy.

The study population designed to be enrolled is patients with histologically and/or cytologically confirmed breast cancer with clinical evidence of recurrent or progressive HER2-negative metastatic disease and planning to begin a chemotherapy regimen of physician's choice for HER2-negative MBC who have evidence of fatigue.

An add-on study design to assess the superiority of TW1025 over placebo will be utilized in this study to evaluate whether TW1025 can decrease fatigue in patients with fatigue. The study will be conducted as a double-blind, randomized trial.

Inclusion Criteria:

• A patient is eligible for the study if all of the following apply:

  1. Female patients at least 18 years of age for study sites in the United States and 20 to 80 years old (inclusive) for study sites in Taiwan
  2. Histologically and/or cytologically confirmed HER2-negative breast cancer with clinical evidence of recurrent or progressive metastatic disease
  3. Patients may have measurable or nonmeasurable metastatic breast cancer.
  4. Planning to begin a new chemotherapy regimen of the physician's choice
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2
  6. HER2-negative disease per College of American Pathologists (CAP) guidelines (immunohistochemistry (IHC) 0, 1+, or if 2+ fluorescence in-situ hybridization (FISH)-negative ratio < 2.0)
  7. Known ER status: ER-negative (0% of cells positive for ER) or ER-positive (≥1% cells positive for ER) by IHC
  8. Adequate bone marrow function (absolute neutrophil count ≥ 1,500 /µL, hemoglobin count ≥ 8 g/dL, and platelet count > 100,000/µL), total serum bilirubin < 1.5 mg/dL and SGOT/SGPT less than 5-times the upper limit of normal if liver metastases are present or < 2.5-times the upper limit of normal if no liver metastases, and serum creatinine < 1.5 mg/dL
  9. Fatigue score of ≥5 on a 1-to-10 linear analog scale
  10. Pain score of ≤4 on a 1-to-10 linear analog scale
  11. Insomnia score of ≤4 on a 1-to-10 linear analog scale
  12. If of childbearing potential, agrees to use reliable contraceptive method(s) during participation in the study
  13. Estimated life expectancy of at least 6 months
  14. Has provided written informed consent and HIPAA authorization

Exclusion Criteria:

• Any patient meeting any of the exclusion criteria will be excluded from study participation:

  1. Has received radiotherapy or cytotoxic therapy within 3 weeks

  2. Any uncontrolled infection

  3. History of lupus erythematosus, rheumatoid arthritis, ankylosing spondylosis, scleroderma, or multiple sclerosis

  4. History of known brain metastases; Screening for brain metastases is not required

  5. More than 4 prior cytotoxic chemotherapy regimens for metastatic disease

  6. Requirement for ongoing systemic steroid therapy

  7. Currently using any other pharmacologic agents or nonpharmacologic interventions to specifically treat fatigue including psychostimulants, antidepressants, acupuncture, etc.

     Note: Antidepressants used to treat items other than fatigue (such as depression or hot flashes) are allowed if the patient has been on a stable dose for ≥ 3 months and plans to continue for ≥ 1 month. Erythropoietin agents to treat anemia are allowed. Exercise is allowed.

  8. Pain requiring long-acting continuous release narcotic pain medication; however, short-acting opioids (oxycodone, hydrocodone), tramadol, and over the counter analgesics such as acetaminophen or NSAIDs are allowed

  9. Use of any over the counter herbal/dietary supplement marketed for fatigue or energy (for example, products containing any type of ginseng, rhodiola rosea, high doses of caffeine, guarana, or anything called an "adaptogen")

  10. Uncontrolled nausea or vomiting or any symptom that would prevent the ability to comply with daily oral TW1025/placebo treatment

  11. Uncontrolled thyroid disorder

  12. Psychiatric disorder such as severe depression, manic depressive disorder, obsessive compulsive disorder or schizophrenia (Defined per medical history)

  13. Any other serious diseases/medical history that would limit the patient's ability to receive study therapy as assessed by the investigator

  14. Lactating, pregnant, or plans to be become pregnant

  15. Has received an investigational agent within 4 weeks of entering this study

  16. History of adverse reactions to any of the ingredients in TW1025.

Each study site has at least three monitors for the study and all of data will send to Data Center in DSG immediately for all study physicians reference.