Orally Administrated JBM-TC4 Prevents Acute Radiodermatitis in Breast Cancer Patients

Phase 2 Study of Orally Administrated JBM-TC4 for the Prevention of Acute Radiation-induced Dermatitis in Breast Cancer Patients

Kaohsiung Medical University Chung-Ho Memorial Hospital, Taipei Veterans General Hospital, Taiwan, Efficient Pharma Management Corp.

This trial is designed as a multicenter, double-blinded, randomized, placebo controlled study to assess the safety and efficacy of JBM-TC4 for the prevention and treatment of acute radiation-induced dermatitis in breast cancer patients receiving radiotherapy.

This study will be conducted in 2 sites in Taiwan. Upon confirmation of meeting all eligibility criteria, will be randomized in a 1:1:1 ratio to 2000 mg or 3000 mg JBM-TC4 oral treatment group or to placebo control group. The treatment will start one week prior to radiotherapy and continue through the radiotherapy period for additional 11 weeks of JBM-TC4. The patients will take 3 treatment capsules twice a day, after breakfast and dinner. Screening visit will occur up to 14 days prior to randomization (Day 0), and informed consent form will be signed and patient eligibility criteria will be verified.Medical history information, chemistry/hematology evaluation, serum pregnancy will be conducted and documented. On Day 0, baseline assessment will be done and study drug will be dispensed. The patients will be instructed to start their study medication after breakfast on Day 1 and record the administration time in the study diary. Post-operative radiotherapy will begin for all patients after taking the treatment for 7 days. On Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 92, data including radiation dermatitis severity, redness and pain scale will be collected when patients return to the clinic for evaluation. On Days 29, 57, 85 and 92, quality of life questionnaire will be completed by patients and blood will be drawn for chemistry/hematology evaluation. The final study visit will occur one week after the last dose of study medication, which will be around Day 92. ECG will be evaluated on Day 8 and 92. A total of 120 women with breast cancer will be recruited into this study. Safety will be assessed through recording of adverse events, assessment of vital signs, and chemistry/hematology laboratory testing. During each clinic visit, investigator will take down the vital signs of the patients and ask if the patients has experienced any adverse events. All information will be recorded on the case report form. The primary efficacy endpoint in this study is to assess the effectiveness of JBM-TC4 for the prevention and treatment of acute radiation-induced dermatitis. The effectiveness will be determined by the recording of the radiation dermatitis severity scale for patients during each weekly study visit. Secondary efficacy endpoint include 1) Presence of moist desquamation and 2) redness at the radiation treated site at any visit. 3)The worst pain related to dermatitis between baseline and follow-up visit at the radiotherapy site. 4) Quality of life and 5) safety evaluation assessment. At the final visit, each investigator will be ask to rate their patients' responses to treatment.

Totally 2000 mg of JBM-TC4 per day. 2 capsules of 500 mg JBM-TC4 plus 1 capsule of 500 mg PEG-400 per time, twice a day.

2 capsules of 500 mg JBM-TC4 plus 1 capsule of 500 mg PEG-400, oral route per time twice a day in Day (-7) prior to radiotherapy and continue through the radiotherapy period for additional 11 weeks.

3 capsules of 500 mg JBM-TC4, oral route per time twice a day in Day (-7) prior to radiotherapy and continue through the radiotherapy period for additional 11 weeks.

3 capsules of 500 mg polyethylene glycol 400 (PEG-400), oral route per time twice a day in Day (-7) prior to radiotherapy and continue through the radiotherapy period for additional 11 weeks.

During each weekly visit (Day 0,8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 86 and 92), starting from baseline evaluation at Day 0, the severity of radiodermatitis in breast cancer patients at the radiotherapy site will be assess by the investigator using the RDS (CTCAE 4.03), which the ranges from 0 to 5 with increments of 1.

The presence of moist desquamation information will be obtained from RDS score at 0,8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 86, 92 days. Patients with score 3 or more will be recorded as having moist desquamation on the radiotherapy site.

Score of redness at the radiotherapy site will be evaluated at all the visits starting from Day 0 along with RDS scale (at 0,8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 86, 92 days).

Starting on Day 0, patients will be ask to circle a number that best describe the worst pain related to dermatitis they have been experiencing through the past week. (at 0,8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 86, 92 days)

Quality of life is measured using the Quality of Life Questionnaire. Patients will select the response that best describe their conditions at Day 0, 29, 57, 85 and 92. Scores will be calculated ans transcribed scores will be collected on the case report forms.

Blood pressure and pulse rate will be measured in the writing arm and recorded to mmHg or beat per minute, respectively. The same arm will be used through this study. They will be measured after 5 minutes supine and 2 minutes standing. Oral temperature, recorded to the nearest 0.1 degree Celsius, will be measured during the supine vital sign measurements. All above will be obtained at Day 0,8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 86 and 92.

A 12-lead ECG will be obtained on all subjects at the designed times (Fay 0, 8, 29, 57 and 85) in the flow charts.

During the visits on Days 0, 29, 57, 85 and 92, the blood samples will be drawn for routine laboratory evaluations. The parameters includes hemoglobin, hematocrit, white blood count with differential, platelet count, red blood cell count, Glutamate-oxaloacetate transaminase, Glutamic-Pyruvic Transaminase, blood urea nitrogen, creatinine, cholesterol, HDL, LDL, triglyceride, blood glucose test.. Plasma sample will be collected and frozen at visits days 0, 8 (after ECG collection), 29, 57 and 85 for future assay of pharmacokinetics.

All adverse events, regardless of seriousness, severity, or presumed relationship to study drug, are events that occur between the day of with the informed consent is signed and completion of the treatment phase. They must be recorded using medical terminology in the source document and the Case Report Form. Graphical techniques may also be used to examine the relationship between these measures and dose and to investigate any trends in the data. Incidence rates for all adverse events , and the number of subjects withdrawing from the study for each reason will be tabulated.

Inclusion Criteria: males or non-pregnant females at least 20 year of age. Diagnosis of, non-inflammatory breast adenocarcinoma and be referred for post-operative radiotherapy without concurrent chemotherapy. Breast adenocarcinoma previously treated by lumpectomy with or without adjuvant or neoadjuvant chemotherapy or hormonal treatment. With in situ breast cancer are also eligible Prescribed concurrent hormone treatment with radiation treatment Participants must be scheduled to receive 5 sessions of radiotherapy per week (1 session per day) for at least 5 weeks using standard (1.8 Gy to 2.0 Gy per session) for total dose of at least 45 Gy. A time period of 3 weeks must elapse after chemotherapy and surgery before beginning this study. Must be able to swallow medication. Participant must give informed consent. Exclusion Criteria: Bilateral breast cancer Previous radiotherapy to the breast or chest. Chemotherapy cocurrent with radiation treatment. Receiving treatment with anti-coagulants, or anti-human epidermal growth factor receptor drugs, e.g., Iressa (gefitinib), Erbitux (cetuximab, C225), concurrently with their radiotherapy. Prior breast reconstructions, implants, and/or expanders. Known radiosensitivity syndromes, e.g., Ataxia-telangiectasia. Collagen vascular disease, vasculitis, unhealed surgical sites, breast infections, or systemic lupus erythematosus. Baseline blood tests that meet the following criteria: Grade 2 change in hemoglobin (i.e., 25% decease from baseline); Grade 1 change in platelets (i.e., < 75'000/mm3); Grade 2 change in prothrombin time and partial thromboplastin time (i.e., 1.5-2x upper limit of normal); Grade 1 change in aspartate transaminase, alanine transaminase (i.e., > 2.5x upper limit of normal); Grade 1 change in bilirubin (i.e., > 1.5x upper limit of normal); Grade 1 change in Creatinine (i.e., > 2x upper limit of normal). Conditions affecting the absorption for oral medications.

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