Clinical trial NCT05244577: Olanzapine Combined With Fosaprepitant, Ondansetron, and Dexamethasone for Preventing Nausea and Vomiting in Patients With Testicular Cancer
Official title: A Phase III Randomized, Double-blind, Placebo-controlled, Cross-over Study to Evaluate Olanzapine Combined With Fosaprepitant, Ondansetron, and Dexamethasone for Preventing Nausea and Vomiting in Patients With Testicular Cancer Receiving 5-day Cisplatin Combination Chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Olanzapine
CINV
Testicular Cancer by AJCC V6 and V7 Stage
Cisplatin
Keywords: testicular cancer
olanzapine
Cisplatin 5-day regimen
Nausea and vomiting
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-02-17
Enrollment: 75
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the efficacy and safety of olanzapine combined with fosaprepitant, ondansetron and dexamethasone compared with placebo combined with fosaprepitant, ondansetron and dexamethasone in the prevention of nausea and vomiting in germ-cell tumors receiving 5-day cisplatin chemotherapy

Detailed description: This is a prospective, randomized, double-blind, placebo-controlled, cross-over Phase III clinical study.

A total of 75 patients were enrolled in two sequential treatment groups (olanzapine-placebo and placebo-Olanzapine).

(1) The screening process begins after the patient signs the written informed consent. (2) Patients were randomly divided into control group (placebo) and experimental group (olanzapine). (3) Patients' effectiveness from the beginning of chemotherapy drug infusion (0 h on day 1) to day 10 (approximately 240 h) was monitored by patients' diary from 2 to 10 days after chemotherapy, in which patients should report episodes of vomiting in the previous 24 hours, use of remedial therapy, and assessment of daily nausea. Any episodes of vomiting or retching, as well as the time and date of use of rescue medications, should also be recorded. At days 2 to 6, patients were assessed on the visual analog scale (VAS) for the previous 24 hours. (4) The Hospital Anxiety and Depression Scale (HADS),and Life Index - Vomiting (FLIE) questionnaire of days 1-10 should be completed immediately after the log is completed on day 10. (5) During the study period, patients may receive "remedial treatment" for nausea or vomiting, and patients requiring remedial treatment are considered to have failed treatment because the primary endpoint is complete remission. However, patients receiving remedial treatment must continue to receive the study drug and complete the diary as directed.

Eligibility criteria: Inclusion Criteria

Patients must meet the following criteria for inclusion:

1. Pathology confirmed germ cell tumor (both spermatogonoma and non-spermatogonoma) and had no chemotherapy before;
2. Men;
3. Age ≥16 years old;
4. ECOG score of physical status 0-2;
5. Chemotherapy regimen containing 5-day cisplatin (20mg/m2, 100mg total;
6. No other nausea, vomiting, or use of any antiemetics within 72 hours prior to enrollment;
7. There are no clear brain metastases or other reasons for long-term systemic use of hormones;
8. The general condition is good, and the blood, liver and kidney functions meet the following standards:

   Hemoglobin: 90 g/L and above White blood cell count: 3.5 \* 109 / L - 10.0 \*109 / L Neutrophil count: 1.5\* 109/L or above Platelet count: 90\* 109/L or above Serum total bilirubin: below 1.5 times the upper limit of normal Serum AST, ALT and ALP: the upper limit of normal is below 2.5 times when the patient is present
9. Ability to read, understand and complete research questionnaires and journals, including visual analog scale (VAS);
10. Understand the study procedure and sign the informed consent in person to participate in the study

Exclusion Criteria

Patients who meet any of the following criteria will be excluded:

1. Digestive tract obstruction, water and electrolyte disorder;
2. Have central nervous system diseases (such as primary brain tumors, uncontrolled seizures, any history of brain metastases or strokes);
3. Contraindications to the use of glucocorticoids: ① Viral, bacterial, fungal and other infections that cannot be controlled by antibiotics;② Active gastric or duodenal ulcer;③ Severe hypertension, arteriosclerosis, diabetes; ④ Osteoporosis;⑤ Corneal ulcer;⑥Trauma or surgical repair period, fracture; ⑦Adeno-cortical hyperfunction; ⑧Severe mental illness and epilepsy; ⑨ patients with cardiac or renal dysfunction;
4. Patients with mental disabilities or severe emotional or mental disorders are considered unsuitable for inclusion in the study;
5. In addition to malignancy, the patient has an active infection (e.g. pneumonia, hepatitis) or any uncontrolled infection diseases (such as diabetic ketoacidosis), and the researchers believe may contribute to the study's findings confounding, or exposing patients receiving study drugs to unnecessary risks;
6. The patient is currently using any prohibited drugs, including medicinal marijuana or is currently using alcohol (Chinese Diagnostic criteria for drug dependence);
7. The patient received an unapproved (experimental) drug treatment within the past 4 weeks;
8. Taking oral olanzapine or other psychotropic drugs;
9. A history of hypersensitivity to fosappitan, 5-HT3 receptor antagonists or dexamethasone;
10. The patient cannot swallow the drugs;
11. The principal investigator considered the patients unsuitable for the study;
12. Inability or unwillingness to adhere to research protocols

Primary outcomes:
measure: Percentage of Participants With Complete Response From 0 to 240 Hours After Initiation chemotherapy
timeFrame: 1 to 10 days
Secondary outcomes:
measure: Percentage of Participants With minimal nausea
timeFrame: 1-10 days
measure: Percentage of Participants with total control
timeFrame: 1 to 10 days
measure: Severity of nausea
timeFrame: 1 to 10 days
measure: Number of rescue medications
timeFrame: 1 to 10 days
measure: Time to Treatment Failure in each group of participates
timeFrame: 1 to 10 days
measure: Patient's satisfaction with anti-emetic therapy
timeFrame: 1 to 10 days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yanxia Shi, PHD
role: PRINCIPAL_INVESTIGATOR
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