Olanzapine Against Delayed Nausea and Vomiting in Women Receiving Carboplatin Plus Paclitaxel

Study Overview
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Brief Summary
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This randomized, pilot study explores the activity of olanzapine with or without delayed dexamethasone for the prevention of delayed nausea and vomiting in women with gynecologic cancer receiving the combination of carboplatin and paclitaxel. Women treated with this regimen are particularly susceptible to chemotherapy-induced nausea and vomiting. Given anti-emetic prophylaxis with olanzapine may increase the control of delayed symptoms in women receiving carboplatin and paclitaxel.

Detailed Description
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The purpose of this study is to assess if the use of olanzapine can improve control of delayed nausea and vomiting in women receiving the combination of carboplatin and paclitaxel for a gynaecologic cancer. Patients are randomized to one of three treatment arms. Please see the Arms and Intervention sections for more detailed information. The primary objective is to determine in each treatment group the proportion of patients achieving Complete Protection (CP; no vomiting, no rescue anti-emetics, and no more than mild nausea) during the delayed phase (days 2-5 post-chemotherapy) in the first chemotherapy cycle. The secondary objectives are: To determine the proportion of patients achieving Complete Response (CR; no vomiting, and no rescue anti-emetics) during the acute (day 1 post-chemotherapy), delayed, and overall (days 1-5 post-chemotherapy) periods. To determine the incidences of potential toxicities ascribed to olanzapine. To assess the impact of nausea and vomiting on daily life activities in each treatment group. Protocol treatment is to begin ≤14 days of registration. Patients will receive treatment on Days 1-3. Patients will be permitted to take rescue therapy of the treating investigator's choice based on the clinical circumstances. After completing treatment, patients will be monitored for side effects.

Official Title
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Olanzapine for the Prevention of Delayed Nausea and Vomiting in Patients With Gynecologic Cancers Receiving Carboplatin and Paclitaxel-based Chemotherapy and Guideline-directed Prophylactic Anti-emetics

Conditions
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Nausea, Vomiting

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented gynaecologic cancer Patients who are chemotherapy naive and scheduled to receive 1-day moderately emetogenic chemotherapy (carboplatin Area under Curve (AUC) 5 plus paclitaxel). Women, 18 years and older Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 Adequate organ system function, defined as follows: bone marrow: absolute neutrophil count >=1,500/L, platelets >=100,000/L liver: bilirubin 1.5 x upper limit of normal (ULN); transaminases <=2.5 x ULN kidney: creatinine <=1.5 x ULN • Able to take oral medications Exclusion Criteria: psychiatric illness or social situation that would preclude study compliance history of central nervous system (e.g., brain metastases, seizure disorder) Positive pregnancy test just before registration. treatment with any anti-emetic medication from 24 hours to 5 days after treatment. treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone for 30 days before or during protocol therapy. concurrent abdominal radiation therapy. concurrent quinolone antibiotic therapy. known hypersensitivity to olanzapine. vomiting and/or significant nausea (>= Common Toxicity Criteria for Adverse Events (CTCAE) grade 2) within the 24 hours before beginning chemotherapy. another organic cause for nausea or vomiting unrelated to chemotherapy administration. chronic alcoholism (as determined by the investigator). known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the previous 6 months. history of uncontrolled diabetes mellitus.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: olanzapine Days 1-3<br>Olanzapine + Chemotherapy + Antiemetic treatment Patients will receive the chemotherapy drugs carboplatin and paclitaxel as well as the following anti-nausea/vomiting drugs: Palonosetron (0.25 mg intravenously) on the day of chemotherapy, plus Dexamethasone (16 mg intravenously on the day of chemotherapy), plus Olanzapine (10 mg orally on the day of chemotherapy and 10 mg orally on days 2, 3 post chemotherapy) | Drug: Olanzapine<br>* Drug: Olanzapine 10 mg oral Drug: Chemotherapy (carboplatin and paclitaxel). Patients will receive carboplatin and paclitaxel. Drug: Anti-emetic treatment (palonosetron; plus dexamethasone). Palonosetron (0.25 mg IV) on the day of chemotherapy plus dexamethasone (16 mg IV on the day of chemotherapy and 8 or 4 mg (depending on the experimental arm) oral on days 2 and 3 post-chemotherapy).<br>* Other names: Paclitaxel;Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine<br>* all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1<br>|
| Experimental: olanzapine+Dexamethasone d 1-3<br>Olanzapine + Chemotherapy + Antiemetic treatment Patients will receive the chemotherapy drugs carboplatin and paclitaxel as well as the following anti-nausea/vomiting drugs: Palonosetron (0.25 mg intravenously) on the day of chemotherapy, plus Dexamethasone (16 mg intravenously on the day of chemotherapy and 4 mg orally days 2, 3 post chemotherapy), plus Olanzapine (10 mg orally on the day of chemotherapy and 10 mg orally on days 2, 3 post chemotherapy) | Drug: Olanzapine<br>* Drug: Olanzapine 10 mg oral Drug: Chemotherapy (carboplatin and paclitaxel). Patients will receive carboplatin and paclitaxel. Drug: Anti-emetic treatment (palonosetron; plus dexamethasone). Palonosetron (0.25 mg IV) on the day of chemotherapy plus dexamethasone (16 mg IV on the day of chemotherapy and 8 or 4 mg (depending on the experimental arm) oral on days 2 and 3 post-chemotherapy).<br>* Other names: Paclitaxel;Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine<br>* all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1<br>|
| Active Comparator: dexamethasone days 1-3<br>Dexamethasone + Chemotherapy + Antiemetic treatment Patients will receive the chemotherapy drugs carboplatin and paclitaxel as well as usual anti-nausea/vomiting drugs: Palonosetron (0.25 mg intravenously) on the day of chemotherapy, plus Dexamethasone 16 mg intravenously on the day of chemotherapy (day 1), plus Dexamethasone 8 mg orally on days 2 and 3 post chemotherapy | Drug: Olanzapine<br>* Drug: Olanzapine 10 mg oral Drug: Chemotherapy (carboplatin and paclitaxel). Patients will receive carboplatin and paclitaxel. Drug: Anti-emetic treatment (palonosetron; plus dexamethasone). Palonosetron (0.25 mg IV) on the day of chemotherapy plus dexamethasone (16 mg IV on the day of chemotherapy and 8 or 4 mg (depending on the experimental arm) oral on days 2 and 3 post-chemotherapy).<br>* Other names: Paclitaxel;Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine<br>* all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Protection | Proportion of patients achieving delayed Complete Protection, defined as no vomiting, no rescue anti-emetics, and no more than mild nausea measured by the Nausea and Vomiting Daily Diary/Questionnaire. | days 2-5 post-chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nausea scores | • Nausea scores measured by the Nausea and Vomiting Daily Diary/Questionnaire. | up to 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nausea, Vomiting