Phase II Study of SyB D-0701 for Radiotherapy-Induced Nausea and Vomiting (RINV)

Study Overview
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Brief Summary
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The purpose of this study is to explore the dose response of SyB D-0701 for preventing nausea and emesis associated with radiotherapy (fractionated/localized irradiation) in cancer patients scheduled to receive radiotherapy (fractionated/localized irradiation) alone.

Detailed Description
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Exploratory study of dose response of SyB D-0701 to preventing effects for nausea and emesis associated with radiotherapy (fractionated/localized irradiation)

Official Title
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Phase II Clinical Study of SyB D-0701 for Radiotherapy Induced Nausea and Vomiting

Conditions
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Radiotherapy-induced Nausea and Vomiting (RINV)

Intervention / Treatment
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* Drug: SyB D-0701
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients must satisfy the following conditions listed below. Patients with histologically verified malignant tumors Patients receiving radiotherapy alone who are scheduled for at least 3 fractions, each at a radiation dose of 1.5 to 3.0 Gy Cancer patients scheduled for radiotherapy over a field of at least 100 cm2 (50 cm2 or more in cases of irradiation of the vertebrae only) that includes the abdomen and pelvis (region with upper edge at the 11th thoracic vertebrae and lower edge at pelvic cavity) Patients not scheduled to receive anti-tumor agents between the first and the fifth day of radiotherapy. If the patient has a history of anti-tumor agent therapy, however, at the time of the patient's registration, at least 5 days must have elapsed since drug administration was terminated, and the patient must not be scheduled to receive any anti-tumor agent from the first to the fifth day of radiotherapy Male patients who are surgically sterilized, or who agree to practice adequate contraception during the study Female patients of child-bearing potential who agree to practice adequate contraception during the study Patients whose performance status (PS) of Eastern Cooperative Oncology Group (ECOG) is 0 to 2 Patients who were at least 20 years of age when their consent was obtained Patients who have given consent in writing to participate in the study with full understanding of the explanatory documents Exclusion Criteria Patients who satisfy any of the following conditions will not be enrolled in the study. Patients with nausea and/or emesis; patients who also have intestinal obstruction, vestibular dysfunction (e.g., epilepsy), Meniere's syndrome, cerebral metastasis, electrolyte imbalance (hypercalcemia, hyperglycemia, hyponatremia), uremia, etc., and patients for whom it is judged that there is a high probability that their nausea or emesis arises from the aforementioned causes. Registration is possible, however, for patients with motion sickness (vehicle sickness) or patients with temporary nausea/emesis arising from routine activities. Patients with primary or metastasized brain tumors who show signs of elevated intracranial pressure Patients who previously received radiotherapy to the brain or to the region that includes the abdomen and pelvis (region with upper edge at the 11th thoracic vertebrae and lower edge at pelvic cavity) Patients who take drugs that affect the evaluation of nausea or emesis (rescue medication and 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, neurokinin 1 (NK1) receptor antagonists, anxiolytics, psychotropic drug, opioid analgesics and corticosteroid [systemic administration] except for rescue medication) Patients with abnormal findings (e.g., erythema, rash, wounds) at sites where the study drug has been applied Patients with a history of hypersensitivity to study drug ingredients or to other 5-HT3 receptor antagonists Patients with a history of allergy involving dermal symptoms Patients with clear signs of infection (including viral infection) Patients with complications from drug or alcohol dependence, or with a history of the same Patients who have participated in some type of clinical study (including physician-initiated clinical studies or clinical research) within 3 months prior to their registration for the present study and who have been given a study drug (including drugs not yet approved). Patients can be registered for this study, however, if they have participated in a clinical study, etc., in which only drugs already approved have been used. Patients with serious hepatic or renal damage [Grade 3 or above in the Common Terminology Criteria for Adverse Events (CTCAE) (ver. 4.0-JCOG)] Patients with cardiac dysfunction Patients who are pregnant, who might be pregnant or who are currently lactating Other patients judged as unsuitable by the investigator or sub-investigators

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SyB D-0701: high dose group<br> | Drug: SyB D-0701<br>* Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch, High dose group (30.00 mg): SyB D-0701 15 cm2 patch + SyB D-0701 25 cm2 patch] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.<br>|
| Experimental: SyB D-0701: low dose group<br> | Drug: SyB D-0701<br>* Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch, High dose group (30.00 mg): SyB D-0701 15 cm2 patch + SyB D-0701 25 cm2 patch] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.<br>Drug: Placebo<br>* Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.<br>|
| Placebo Comparator: placebo group<br> | Drug: Placebo<br>* Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Control (no Signs of Emesis or Moderate to Severe Nausea and no Use of Rescue Medication) Rate From the Start of Radiotherapy Until 24 Hours After the Third Irradiation | The complete control rate was defined as the percentage of subjects who had no emesis and no moderate or more severe nausea and who used no rescue drugs during the period from the time of the first irradiation to 24 hours after the third irradiation. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (no Signs of Emesis and no Use of Rescue Medication) Rate From the Start of Radiotherapy Until 24 Hours After the Third Irradiation | The complete response rate was defined as the percentage of subjects who had no emesis and who used no rescue drugs during the period from the time of the first irradiation to 24 hours after the third irradiation. | 72 hours | 
| Time to First Emesis | Time from the start of radiotherapy to the onset of first emesis. The median (50% point) of time to first emesis was estimated. | 24-72 hours | 
| Time to First Nausea | Time from the start of radiotherapy to the onset of first nausea. The median (50% point) of time to first nausea was estimated. | 24-72 hours | 
| Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Complete control rate within 24 hours after each irradiation, from the first to the third fraction of radiotherapy. The complete control rate was defined as the percentage of subjects who had no emesis and no moderate or more severe nausea and who used no rescue drugs. | 24-72 hours | 
| Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Complete response rate within 24 hours after each irradiation, from the first to the third fraction of radiotherapy. The complete response rate was defined as the percentage of subjects who had no emesis and who used no rescue drugs. | 24-72 hours | 
| Adverse Events | Adverse event is any untoward medical occurrence experienced by a subject irrespective of causal relationship with the study drug, and includes the unexpected signs, clinically significant fluctuations of laboratory data, and aggravation of disease, symptoms or complications. Adverse events are coded using the preferred terms (PT) of Medical Dictionary for Regulatory Activities (MedDRA) version 15.0. | Up to 192 hours | 
| Severe (Grade 3 or More) Adverse Events | The severity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, Grade 5: Death related to AE | Up to 192 hours | 
| Skin Manifestations at Study Drug Application Site | The investigator or sub-investigator recorded skin manifestations observed after removal of the study drug. Skin manifestations were counted for each type of patches (placebo patch, SyB D-0701 15 cm2 patch, SyB D-0701 25 cm2 patch). | Up to 192 hours |