Olanzapine Combined With Fosaprepitant, Ondansetron, and Dexamethasone for Preventing Nausea and Vomiting in Patients With Testicular Cancer

Cisplatin Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05244577
• Other study ID #: 2021-FXY-268
• Status: Recruiting
• Phase: Phase 3
• Start date: January 18, 2022
• Est. completion date: March 31, 2024

Study information

• Verified date: February 2023
• Source: Sun Yat-sen University
• Contact: Yanxia Shi, PHD
• Phone: +8613609058827
• Email: shiyx[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: March 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years and older

Eligibility

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: ? Viral, bacterial, fungal and other infections that cannot be controlled by antibiotics;? Active gastric or duodenal ulcer;? Severe hypertension, arteriosclerosis, diabetes; ? Osteoporosis;? Corneal ulcer;?Trauma or surgical repair period, fracture; ?Adeno-cortical hyperfunction; ?Severe mental illness and epilepsy; ? 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

Related Conditions & MeSH terms

• CINV
• Cisplatin
• Nausea
• Olanzapine
• Testicular Neoplasms
• Vomiting

Intervention

Drug:
• Olanzapine Tablets
Olanzapine,Ondansetron,Dexamethasone,Fosaprepitant
• Placebo
Placebo,Ondansetron,Dexamethasone,Fosaprepitant

Locations

Country	Name	City	State
China	Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shi Yanxia

Country where clinical trial is conducted

China, 

References & Publications (9)

Albany C, Brames MJ, Fausel C, Johnson CS, Picus J, Einhorn LH. Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. J Clin Oncol. 2012 Nov 10;30(32):3998-4003. doi: 10.1200/JCO.2011.39.5558. Epub 2012 Aug 20. — View Citation

Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501. doi: 10.1200/JCO.2010.31.7859. Epub 2011 Mar 7. — View Citation

Hashimoto H, Abe M, Tokuyama O, Mizutani H, Uchitomi Y, Yamaguchi T, Hoshina Y, Sakata Y, Takahashi TY, Nakashima K, Nakao M, Takei D, Zenda S, Mizukami K, Iwasa S, Sakurai M, Yamamoto N, Ohe Y. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Feb;21(2):242-249. doi: 10.1016/S1470-2045(19)30678-3. Epub 2019 Dec 11. Erratum In: Lancet Oncol. 2020 Feb;21(2):e70. — View Citation

Herman TS, Einhorn LH, Jones SE, Nagy C, Chester AB, Dean JC, Furnas B, Williams SD, Leigh SA, Dorr RT, Moon TE. Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. N Engl J Med. 1979 Jun 7;300(23):1295-7. doi: 10.1056/NEJM197906073002302. — View Citation

Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ; Aprepitant Protocol 052 Study Group. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin--the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003 Nov 15;21(22):4112-9. doi: 10.1200/JCO.2003.01.095. Epub 2003 Oct 14. — View Citation

Ioroi T, Furukawa J, Kume M, Hirata S, Utsubo Y, Mizuta N, Miyake H, Fujisawa M, Hirai M. Phase II study of palonosetron, aprepitant and dexamethasone to prevent nausea and vomiting induced by multiple-day emetogenic chemotherapy. Support Care Cancer. 2018 May;26(5):1419-1423. doi: 10.1007/s00520-017-3967-2. Epub 2017 Nov 16. — View Citation

Olver IN, Grimison P, Chatfield M, Stockler MR, Toner GC, Gebski V, Harrup R, Underhill C, Kichenadasse G, Singhal N, Davis ID, Boland A, McDonald A, Thomson D; Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Results of a 7-day aprepitant schedule for the prevention of nausea and vomiting in 5-day cisplatin-based germ cell tumor chemotherapy. Support Care Cancer. 2013 Jun;21(6):1561-8. doi: 10.1007/s00520-012-1696-0. Epub 2012 Dec 30. — View Citation

Schmoll HJ, Aapro MS, Poli-Bigelli S, Kim HK, Park K, Jordan K, von Pawel J, Giezek H, Ahmed T, Chan CY. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006 Jun;17(6):1000-6. doi: 10.1093/annonc/mdl019. Epub 2006 Mar 8. — View Citation

Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 May;70(3):145-164. doi: 10.3322/caac.21601. Epub 2020 Mar 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Complete Response From 0 to 240 Hours After Initiation chemotherapy	Complete Response was defined as no vomiting and no use of rescue medication	1 to 10 days
Secondary	Percentage of Participants With minimal nausea	Minimal nausea was defined as <25 mm on a visual analog scale	1-10 days
Secondary	Percentage of Participants with total control	total control was defined as no vomiting, no rescue antiemetics, and no nausea	1 to 10 days
Secondary	Severity of nausea		1 to 10 days
Secondary	Number of rescue medications	Number of rescue medications for nause and vormitting	1 to 10 days
Secondary	Time to Treatment Failure in each group of participates	Time to treatment failure was defined as time to 1st emetic episode or use of rescue medication	1 to 10 days
Secondary	Patient's satisfaction with anti-emetic therapy	The patient was asked to evaluate his satisfaction with the control of nausea and vomiting by recording two scales: Hospital Anxiety and Depression Scale and The Functional Living Index-Emesis questionnaire	1 to 10 days