Evaluate the Safety Profile and Ability of TW1025 Oral Solution to Decrease Fatigue

A Randomized, Double-blind, Placebo-controlled, Parallel Study to Evaluate the Safety Profile and Ability of TW1025 to Decrease Fatigue

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.

Study Overview

• Status: Terminated
• Conditions: Fatigue; Metastatic Breast Cancer
• Intervention / Treatment: Dietary supplement: TW1025; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TW1025; TW1025 oral solution, 20ml, 3 times per day (daily dose: 60 ml)	Dietary supplement: TW1025; 20ml, 3 times per day (daily dose: 60 ml); Other Names: Linease oral solution
Placebo Comparator: Placebo; TW1025 oral solution matched placebo, 20ml, 3 times per day	Dietary supplement: Placebo; 20ml, 3 times per day (daily dose: 60 ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fatigue scores at 9 weeks post-supplement initiation (+/- 1 week) compared with baseline	Change in fatigue scores at 9 weeks post-initiation of supplementation with TW1025/Placebo compared with baseline, assessed by using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale	Baseline vs 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events (AEs)	Adverse events (side effects) in each arm will be counted and compared	1 year after discontinuation of study treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fatigue Scores at Baseline vs at 18-weeks	Change in fatigue scores at 18 weeks post-supplement initiation and other on-treatment time points compared with baseline assessed by using the FACIT Fatigue subscale	Baseline vs 18-weeks
Change in Sleepiness Scores	Change in Daytime sleepiness scores, assessed using the Epworth Sleepiness Scale (ESS)	Baseline vs 9 weeks
Change in Quality of Life Scores	Change in Quality of life scores, assessed using the Quality of Life Linear Analog Scale (QOL-LAS)	Baseline vs 9 weeks
Change in Overall Impression	The Subject Global Impression of Change is a 7-point instrument in which the patient rates the change in their overall status since beginning the study drug (ranging from very much better, moderately better, a little better, about the same, a little worse, moderately worse, to very much worse). It has been used extensively for determination of minimally clinically significant differences in numerous oncology clinical trials. Patients will be asked to fill out the Global Impression of Change scale at week 9 after starting study therapy only.	9 weeks
Levels of C-reactive protein in blood	C-reactive protein levels will be measured at baseline, and at weeks 9 and 18 following initiation of dietary supplement.	baseline vs 9-weeks vs 18-weeks
Change in Gene Expression	Change in Whole blood gene expression profiles will be assessed using the NanoString® human immunology and the human inflammation gene panels at baseline and at weeks 9 and 18 of dietary supplementation. RNA-Seq or other methodologies may also be utilized to evaluate cytokine and immune cell signaling pathways	Baseline vs 9-weeks vs 18-weeks

Collaborators and Investigators

• Sponsor: Meriyana Bio Inc.
• Collaborators: US Oncology Research
• Investigators: Study Chair: Joyce O'Shaughnessy, MD, Texas Oncology-Baylor Charles A. Sammons Cancer Center; Study Director: Jacqueline Whang-Peng, MD., Director, Division of Cancer Center, Wan Fang Hospital, Taiwan; Principal Investigator: Anderson Thomas, MD, Texas Oncology-Bedford; Principal Investigator: Danso Michael, MD, Virginia Oncology Associates; Principal Investigator: Encarnacion Carlos, MD, Texas Oncology-Waco; Principal Investigator: Fleischauer Scott, MD, Texas Oncology-Arlington North; Principal Investigator: Taguchi Julie, MD, Sansum Clinic; Principal Investigator: Wang Grace, MD, Baptist Health Medical Group Oncology, LLC; Principal Investigator: Holmes Frankie, MD, Texas Oncology-Memorial City; Principal Investigator: Houck William, MD, Shenandoah Oncology, P.C.; Principal Investigator: Crane Gregory, MD, The University of Kansas Cancer Center; Principal Investigator: Tsai Michaela, MD, Minnesota Oncology Hematology, P.A.; Principal Investigator: Vukelja Svetislava, MD, Texas Oncology-Tyler; Principal Investigator: Lee Jae, MD, Willamette Valley Cancer Institute and Research Center; Principal Investigator: Smith II John, MD, Northwest Cancer Specialists, P.C.

Publications and helpful links

Helpful Links

• Evaluation of the Safety and Efficacy of THL-P in Metastatic Breast Cancer
• Safety and Efficacy of Tien-Hsien Liquid Practical in Patients with Refractory Metastatic Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase IIa Trial

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: December 22, 2015
• First Submitted That Met QC Criteria: December 30, 2015
• First Posted (Estimate): January 1, 2016

Study Record Updates

• Last Update Posted (Estimate): October 21, 2016
• Last Update Submitted That Met QC Criteria: October 20, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Paclitaxel; docetaxel; eribulin; vinorelbine
• Additional Relevant MeSH Terms: Fatigue
• Other Study ID Numbers: TW1025-2014; 13145 (Other Identifier: US Oncology Research LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.