Trial to Evaluate Efficacy of Olanzapine With Short-acting 5HT3 Inhibitors in Chemotherapy-induced Nausea & Vomiting (CINV) Prophylaxis

Phase 2

• Conditions: Nausea Post Chemotherapy; Nausea; Emesis; Vomiting; Chemotherapy-induced Nausea and Vomiting
• Interventions: Drug: Aprepitant Pill; Drug: Olanzapine; Drug: Ondansetron; Drug: Dexamethasone

• Registration Number: NCT03478605
• Lead Sponsor: Blokhin's Russian Cancer Research Center

Brief Summary

Olanzapine-containing regimens for CINV prophylaxis may provide even better protection than aprepitant-containing regimens.

Detailed Description

Olanzapine-containing regimens for CINV provide high complete response (CR) rate in patients receiving high emetogenic chemotherapy. Olanzapine may be more effective than aprepitant in this setting but cheaper. However, there is no strong evidence supporting the advantages of olanzapine over aprepitant - and this is the reason why aprepitant is still the standard of care. Due to high cost aprepitant can be not affordable in low- and middle income countries; this compromises quality of life of cancer patients. On the other hand, recommended olanzapine-based regimen includes palonosetron, whose price is quite high as well and undesired sedation is a common side effect for olanzapine doses that currently recommended, these adverse events precludes wide use of olanzapine in oncology. Development of effective, tolerable and affordable regimen for CINV prophylaxis based on low-dose olanzapine and short-acting 5-HT3 inhibitors can improve quality of care for many cancer patients.

Study Timeline

• Study First Submitted: 2018-03-14
• Study First Submitted QC: 2018-03-20
• Study First Posted: 2018-03-27
• Study Start: 2018-05-25
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-02
• Last Update Posted: 2018-07-05
• Primary Completion: 2019-05-25
• Study Completion: 2019-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. High-emetogenic chemotherapy (HEC) regimen (e.g., cisplatin ≥70 mg/m2 or doxorubicin ≥60 mg/m2 or carboplatin AUC≥4). Patients that are prescribed less doses of mentioned agents are still allowed if another high-emetogenic drug will be administered (eg, doxorubicin plus cisplatin);
2. Administration of HEC component only in first day of the cycle;
3. No previous chemotherapy or radiotherapy;
4. No concomitant quinolone antibiotics administration;
5. ECOG PS ≤2;
6. No nausea and vomiting 24 hours before enrollment;
7. Adequate hepatic and renal function (eg, ALaT, ASaT ≤3 ULN, creatinine clearance ≥50 ml/minute).
8. No brain metastases, leptomeningeal carcinomatosis, and chronic diseases such as uncontrolled diabetes mellitus and chronic alcohol consumption.
9. Subject willing to participate in the trial and provided informed consent form.

Exclusion Criteria

1. Previous chemotherapy or radiotherapy;
2. Moderate- or low- emetogenic chemotherapy;
3. Multiday administration of HEC agents;
4. ECOG PS >2;
5. History of brain metastases, signs of symptoms of bowel obstruction;
6. Nausea and/or vomiting of any genesis 24 hours before enrollment;
7. Uncontrolled diabetes mellitus or other metabolic diseases; chronic alcohol consumption.
8. Diseases and conditions interfere with subject ability to swallow the drug and to take oral medication;
9. Concomitant therapy with olanzapine or other antipsychotic drugs; history of mental illness;
10. Concomitant therapy with quinolone antibiotics;
11. Contraindications for olanzapine or aprepitant administration;
12. Intraperitoneal or intrapleural administration of HEC drugs;
13. Inadequate hepatic and/or renal function.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aprepitant	Aprepitant Pill	Aprepitant 125 mg p.o d 1 + 80 mg p.o d 2,3 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d. IM or P.O. d 2-4;
Olanzapine	Olanzapine	Olanzapine 5 mg/day p.o. d 0-4 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d.; IM or P.O. d 2-4;
Olanzapine	Ondansetron	Olanzapine 5 mg/day p.o. d 0-4 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d.; IM or P.O. d 2-4;
Olanzapine	Dexamethasone	Olanzapine 5 mg/day p.o. d 0-4 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d.; IM or P.O. d 2-4;
Aprepitant	Ondansetron	Aprepitant 125 mg p.o d 1 + 80 mg p.o d 2,3 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d. IM or P.O. d 2-4;
Aprepitant	Dexamethasone	Aprepitant 125 mg p.o d 1 + 80 mg p.o d 2,3 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d. IM or P.O. d 2-4;

Primary Outcome Measures

Name	Time	Method
Nausea control	0-120 hours after chemotherapy	Complete control of nausea (ie, no nausea) in overall treatment period (0-120 hours after chemotherapy).

Secondary Outcome Measures

Name	Time	Method
Rate of undesired sedation	0-120 hours after chemotherapy	Rate of undesired sedation 0-120 hours after chemotherapy
Complete Response Rate in Acute Treatment Period	0-24 hours after chemotherapy	Complete response rate (ie, no vomiting, no use of rescue medication) in 0-24 hours after chemotherapy
Complete Response Rate in Delayed Treatment Period	24-120 hours after chemotherapy	Complete response rate (ie, no vomiting, no use of rescue medication) in 24-120 hours after chemotherapy
Complete Response Rate in Overall Treatment Period	0-120 hours after chemotherapy	Complete response rate (ie, no vomiting, no use of rescue medication) in 0-120 hours after chemotherapy

Trial Locations

Locations (1)

N.N. Blokhin Cancer Research Center; 🇷🇺 Moscow, Russian Federation