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Double-blind comparative randomized Japanese trial of triplet standard antiemetic therapies with or without 5mg Olanzapine to prevent chemotherapy induced nausea and vomiting for Breast Cancer patients treated with AC therapy (JTOP-B)

Double-blind comparative randomized Japanese trial of triplet antiemetic therapies with or without 5mg Olanzapine for AC therapy (JTOP-B)

500

The subjects of this study were female patients with primary breast cancer (stage I to III), aged 20 years or older on the day of enrollment, and with an ECOG performance status (PS) of 0-1. The median age of the 246 patients in the olanzapine (OLZ) group was 52 years (range 27-78), with 244 patients with a PS of 0 and 2 patients with a PS of 1. The median age of the 234 patients in the placebo group was 51 years (range 30-85), and all had a PS of 0.

Between October 26, 2020, and November 2, 2022, 500 patients from 15 institutions in Japan were randomly assigned to receive oral OLZ(5mg) or placebo for four days. Nineteen patients did not receive treatment; thus, 481 patients ( 246 in the OLZ group and 235 in the placebo group) were assessed for safety. Of the 481 patients treated, one was excluded from the efficacy analyses because the history of receiving moderate emetogenic chemotherapy (MEC). Therefore, patients ( 246 in the OLZ group and 235 in the placebo group), were included in the modified ITT cohort for efficacy analyses. This study was double-blinded, and stratified by age(<55, >=55) and institution.

Adverse events of grade 3 or higher in the OLZ group were somnolence in 4 patients (1.6%), nausea in 3 patients (1.2%), impaired concentration in 2 patients (0.8%), loss of appetite in 2 patients (0.8%), dysgeusia in 1 patient (0.4%), and increased AST in 1 patient (0.4%), while in the placebo group, nausea in 4 patients (1.7%), vomiting in 2 patients (0.9%), and loss of appetite in 1 patient (0.4%).

The CR rate in the OLZ group (58.1%, N=246) was higher than in the placebo group (35.5%, N=234) (P<0.0001) during all-course. In acute phase (0-24h), The CR rate in the OLZ group (76%) was also higher than in the placebo group (54.7%) (P<0.0001) and in delayed phase (25-120h), the CR rate in the OLZ group (63.3%) was higher than in the placebo group (43.2%) (P<0.0001) as well. Regarding side effects of OLZ, sleepiness was reported more frequently in the OLZ group (64.6%) than in the placebo group (51.9%). No differences in concentration loss were seen (OLZ 40.7% vs. placebo 39.6%).

Five mg post-AC OLZ for four days plus standard triplet antiemetic therapy was significantly more effective than placebo plus triplet therapy and was well tolerated among female breast cancer patients.

Mar. 31, 2025

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCT1031200134

Saito Mitsue

Juntendo University Hospital

3-1-3, Hongo, Bunkyo-ku, Tokyo

mitsue@juntendo.ac.jp

Ozeki Rie

Juntendo University Hospital

3-1-3, Hongo, Bunkyo-ku, Tokyo

+81-3-3813-3111

r.ozeki.gs@juntendo.ac.jp

Complete

Sept. 30, 2020

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

prevention purpose

1) Patients with primary breast cancer Stage I to III
2) Receiving 1st AC therapy
3) Female
4) The age of registration is 20 years or older.
5) ECOG performance status (PS): 0-1
6) No history of chemotherapy with moderate or higher emetic risk.
7) Do not use any of the prohibited drugs within 48 hours before registration.
8) The latest test value within one month before registration satisfies all of the following.
A) T-bil<=2.0mg/dL
B) AST<=100U/L
C) ALT<=100U/L
9) Informed consent is obtained in writing from the patient.

1) Patients with a history of allergy to the drugs or similar compounds used in this study.
2) Patients with nausea and vomiting that require antiemetic measures at the time of registration.
3) Patients who started strong opioid within 48 hours before registration.
4) Patients with a history of one or more of unstable angina, myocardial infarction, cerebral hemorrhage, cerebral infarction, and active gastric/duodenal ulcer within 6 months before enrollment.
5) Patients with convulsive disorders requiring treatment with anticonvulsants.
6) Patients with gastrointestinal obstruction such as gastric pyloric stenosis or intestinal obstruction.
7) Women who are pregnant, breastfeeding or may be pregnant or are not willing to contracept.
8) Patients who have mental illness or psychiatric symptoms that interfere with daily life and are considered to be difficult to participate in the study.
9) Diabetic patients who have been treated with at least one of insulin and oral hypoglycemic agents, and patients with HbA1c (NGSP) of 6.5% or more and HbA1c (JDS) of 6.1% or more at the time of registration. In addition to the prescribed tests, patients who may measure blood glucose and thereby reduce or discontinue dexamethasone will also be excluded.
10) Patients who have smoking habits at the time of registration.
11) In addition, patients who were judged to be unsuitable for participation in this study.

Female

Breast Cancer

Olanzapine as a prevention of CINV for AC therapy

Breast Cancer, Chemotherapy induced nausea and vomiting (CINV)

Antiemetic therapy

Complete Response for all course

1. CR rate for the assessment periods (0-24 h, 25-120 h, 25-168 h and 0-168 h)
2. Complete control rate for the assessment periods (0-24 h, 25-120 h, 25-168 h, 0-120 h and 0-168 h)
3. Total control rate for the assessment periods (0-24 h, 25-120 h, 25-168 h, 0-120 h and 0-168 h)
4. Time to treatment failure
5. Severity of nausea (assessed by the patient's own four-grade categorical scale)
6. Appetite loss (assessed by the patient's own four-grade categorical scale)
7. Sleepiness in the daytime, and the incidence of concentration impairment due to sleepiness (assessed by the patient's own four-grade categorical scale)
8. Subjective evaluation by the patient (refer to PRO-CTCAE & trade Trademark Symbol Japanese version)
Nausea, vomiting, concentration impairment, loss of appetite, unclear (or changed taste) taste of food or drink, dry mouth, hiccups, constipation, diarrhea (loose stool or watery) Stool), dizziness, sleeplessness
9. Adverse event occurrence rate
10. Satisfaction with antiemetic therapy (assessed by the patient's own seven-grade categorical scale)

+81-3-5802-1584

Aug. 25, 2020

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