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

Study Overview
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Brief Summary
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Olanzapine-containing regimens for CINV prophylaxis may provide even better protection than aprepitant-containing regimens.

Detailed Description
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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.

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

Conditions
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Emesis, Vomiting, Nausea Post Chemotherapy, Nausea, Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Aprepitant Pill
* Drug: Ondansetron
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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); Administration of HEC component only in first day of the cycle; No previous chemotherapy or radiotherapy; No concomitant quinolone antibiotics administration; ECOG PS ≤2; No nausea and vomiting 24 hours before enrollment; Adequate hepatic and renal function (eg, ALaT, ASaT ≤3 ULN, creatinine clearance ≥50 ml/minute). No brain metastases, leptomeningeal carcinomatosis, and chronic diseases such as uncontrolled diabetes mellitus and chronic alcohol consumption. Subject willing to participate in the trial and provided informed consent form. Exclusion Criteria: Previous chemotherapy or radiotherapy; Moderate- or low- emetogenic chemotherapy; Multiday administration of HEC agents; ECOG PS >2; History of brain metastases, signs of symptoms of bowel obstruction; Nausea and/or vomiting of any genesis 24 hours before enrollment; Uncontrolled diabetes mellitus or other metabolic diseases; chronic alcohol consumption. Diseases and conditions interfere with subject ability to swallow the drug and to take oral medication; Concomitant therapy with olanzapine or other antipsychotic drugs; history of mental illness; Concomitant therapy with quinolone antibiotics; Contraindications for olanzapine or aprepitant administration; Intraperitoneal or intrapleural administration of HEC drugs; Inadequate hepatic and/or renal function.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase II randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine<br>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; | Drug: Olanzapine<br>* Olanzapine 5 mg/day will be administered orally on days 0-4 of chemotherapy cycle (before bedtime)<br>* Other names: Zyprexa;Drug: Ondansetron<br>* Ondansetron 16 mg IV on day 1 of chemotherapy cycle (as standard component of antiemetic therapy)<br>Drug: Dexamethasone<br>* Dexamethasone 8 mg IV on day 1 of chemotherapy cycle; 8 mg IV or orally on days 2-3 (as standard component of antiemetic therapy)<br>|
| Active Comparator: Aprepitant<br>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; | Drug: Aprepitant Pill<br>* Aprepitant 125 mg orally will be administered on day 1 of chemotherapy cycle; 80 mg - on days 2 and 3.<br>* Other names: Emend;Drug: Ondansetron<br>* Ondansetron 16 mg IV on day 1 of chemotherapy cycle (as standard component of antiemetic therapy)<br>Drug: Dexamethasone<br>* Dexamethasone 8 mg IV on day 1 of chemotherapy cycle; 8 mg IV or orally on days 2-3 (as standard component of antiemetic therapy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nausea control | Complete control of nausea (ie, no nausea) in overall treatment period (0-120 hours after chemotherapy). | 0-120 hours after chemotherapy | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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olanzapine, aprepitant, CINV, nausea, vomiting, nausea and vomiting, antiemetics