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

NCT ID: NCT05244577

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-18
• Study Completion Date: 2024-03-31

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.

Conditions

Olanzapine; CINV; Testicular Cancer by AJCC V6 and V7 Stage; Cisplatin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olanzapine

Ondansetron 8mg IV, D1-5 30 minutes before chemotherapy; Dexamethasone 6mg Po QD, D1-7; Fosaprepitant 150mg IVD D1,4, 60 minutes before chemotherapy; Olanzapine 5mg Po D1-7

Group Type: EXPERIMENTAL

Olanzapine Tablets

Intervention Type: DRUG

Olanzapine,Ondansetron,Dexamethasone,Fosaprepitant

Placebo

Ondansetron 8mg IV, D1-5 30 minutes before chemotherapy; Dexamethasone 6mg Po QD, D1-7; Fosaprepitant 150mg IVD D1,4, 60 minutes before chemotherapy; Placebo 5mg Po D1-7

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo,Ondansetron,Dexamethasone,Fosaprepitant

Interventions

Olanzapine Tablets

Olanzapine,Ondansetron,Dexamethasone,Fosaprepitant

Intervention Type: DRUG

Placebo

Placebo,Ondansetron,Dexamethasone,Fosaprepitant

Intervention Type: DRUG

Other Intervention Names

Olanzapine

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Shi Yanxia

OTHER

Sponsor Role: lead

Responsible Party

Shi Yanxia

Principal Investigator, Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Yanxia Shi, PHD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yanxia Shi, PHD

Role: CONTACT

shiyx@sysucc.org.cn

+8613609058827

Xin An, PHD

Role: CONTACT

anxin@sysucc.org.cn

+8613650798675

Facility Contacts

Yanxia Shi, PHD

Role: primary

shiyx@sysucc.org.cn

13609058827

References

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.

Reference Type: BACKGROUND

PMID: 32133645 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 375088 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14559886 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16524979 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22915652 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29147855 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23274926 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21383291 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31838011 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2021-FXY-268

Identifier Type: -

Identifier Source: org_study_id