Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy

Study Overview
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Brief Summary
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This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. Olanzapine may help prevent chemotherapy-induced nausea and vomiting by blocking brain receptors that appear to be involved in nausea and vomiting.

Detailed Description
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Patients with cancer may receive chemotherapy that may cause nausea and vomiting. The purpose of this study is to determine if the use of olanzapine in combination with antiemetic therapy can significantly reduce nausea and vomiting in a large number of patients receiving chemotherapy. Patients are randomized to one of two treatment arms. Please see the Arms and Intervention sections for more detailed information. The primary objective is to compare the number of patients with no nausea for the acute (0-24 hours post-chemotherapy), delayed (24-120 hours post-chemotherapy) and overall periods (0-120 hours post-chemotherapy) for patients receiving HEC. The secondary objectives are: To compare the complete response (CR) (no emetic episodes and no use of rescue medication) in the acute, delayed and overall periods To compare the incidences of potential toxicities ascribed to olanzapine Protocol treatment is to begin ≤ 14 days of registration. Patients will receive treatment on Days 1-4. Patients will be permitted to take rescue therapy of the treating investigator's choice for nausea and/or emesis/retching, based on clinical circumstances. After completing treatment, patients will be monitored for side effects.

Official Title
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Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) in Patients Receiving Highly Emetogenic Chemotherapy (HEC): A Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Hematopoietic/Lymphoid Cancer, Nausea and Vomiting, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Chemotherapy (cisplatin or cyclophosphamide and doxorubicin)
* Drug: Antiemetic treatment (ondansetron or granisetron or palonosetron; plus dexamethasone; plus fosaprepitant or aprepitant)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Diagnosis of malignant disease No prior chemotherapy and scheduled to receive HEC (either cisplatin-containing regimen or anthracycline + cyclophosphamide [AC]) Cisplatin at a dose of ≥70mg/m^2, with or without other chemotherapy agent(s) OR Anthracycline (60 mg/m^2) plus cyclophosphamide(600 mg/m^2) Age ≥18 years Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2 Required Initial Laboratory Values ≤ 120 days prior to registration Serum Creatinine ≤2.0 mg/dL Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic oxaloacetic transaminase (SGPT) ≤3 x Upper Limit of Normal (ULN) Absolute neutrophil count (ANC) ≥1500/mm^3 No nausea or vomiting ≤ 24 hours prior to registration Negative pregnancy test (serum or urine) done ≤7 days prior to registration, for women of childbearing potential only (per clinician discretion) No severe cognitive compromise No known history of CNS disease (e.g. brain metastases, seizure disorder) No treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone ≤30 days prior to registration or planned during protocol therapy No chronic phenothiazine administration as an antipsychotic agent (patients may receive prochlorperazine and other phenothiazines as rescue anti-emetic therapy) No concurrent use of amifostine No concurrent abdominal radiotherapy No concurrent use of quinolone antibiotic therapy No chronic alcoholism (as determined by the investigator) No known hypersensitivity to olanzapine No known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the previous six months. No history of uncontrolled diabetes mellitus (e.g. on insulin or an oral hypoglycemic agent)

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine + Chemotherapy + Antiemetic treatment<br>Patients will receive the chemotherapy drugs cisplatin or cyclophosphamide and doxorubicin as well as the following anti-nausea/vomiting drugs: Ondansetron (8 mg orally or intravenously) or granisetron (1 mg intravenously or 2 mg orally) or palonosetron (0.25 mg intravenously) on the day of chemotherapy, plus Dexamethasone (12 mg orally on the day of chemotherapy and 8 mg orally days 2, 3, 4 post chemotherapy), plus Fosaprepitant (150 mg intravenously on the day of chemotherapy) or aprepitant (125 mg orally on the day of chemotherapy and 80 mg orally on days 2 and 3 post chemotherapy), plus olanzapine (10 mg orally on the day of chemotherapy and 10 mg orally on days 2, 3, 4 post chemotherapy) | Drug: Olanzapine<br>* oral<br>Drug: Chemotherapy (cisplatin or cyclophosphamide and doxorubicin)<br>* oral or IV<br>Drug: Antiemetic treatment (ondansetron or granisetron or palonosetron; plus dexamethasone; plus fosaprepitant or aprepitant)<br>* oral or IV<br>|
| Active Comparator: Placebo + Chemotherapy + Antiemetic treatment<br>Patients will receive the chemotherapy drugs cisplatin or cyclophosphamide and doxorubicin as well as usual anti-nausea/vomiting drugs: Ondansetron (8 mg orally or intravenously) or granisetron (1 mg intravenously or 2 mg orally) or palonosetron (0.25 mg intravenously) on the day of chemotherapy, plus Dexamethasone (12 mg orally on the day of chemotherapy and 8 mg orally days 2, 3, 4 post chemotherapy), plus Fosaprepitant (150 mg intravenously on the day of chemotherapy) or aprepitant (125 mg orally on the day of chemotherapy and 80 mg orally on days 2 and 3 post chemotherapy), plus placebo | Drug: Chemotherapy (cisplatin or cyclophosphamide and doxorubicin)<br>* oral or IV<br>Drug: Antiemetic treatment (ondansetron or granisetron or palonosetron; plus dexamethasone; plus fosaprepitant or aprepitant)<br>* oral or IV<br>Other: Placebo<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With no Nausea | No nausea was defined as a response of 0 in the nausea item of Nausea and Vomiting Daily Diary/Questionnaire in the acute (0-24 hours), delayed (25-120 hours) and overall (0-120 hours) periods after chemotherapy. | 0 to 120 hours after chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Nausea Scores | Nausea scores was measured using a visual-analogue scale ranging from 0 (none) to 10 (as bad as it can be). | Baseline and Day 2 to Day 6 after chemotherapy | 
| Proportion of Patients With Complete Response | Complete response was defined as no emetic episodes and no use of rescue medication during the acute (0-24 hours), delayed (25-120 hours) and overall (0-120 hours) periods as measured by the Nausea and Vomiting Daily Diary/Questionnaire. | 0 to 120 hours after chemotherapy | 
| Mean Scores of Potential Toxicities Related to Olanzapine as Measured by the Nausea and Vomiting Daily Diary/Questionnaire | Patients were asked to record daily levels of undesired sedation and appetite increase using a visual-analogue scale ranging from 0 (none) to 10 (as bad as it can be). | Baseline and day 2 to 6 days after chemotherapy | 
| Frequency of Rescue Medication | Patients were asked to record daily number of extra nausea/vomiting pills taken because they developed nausea/vomiting in the following categories: None, One, Two, More than two in Nausea and Vomiting Daily Diary Questionnaire. | Day 2 to Day 6 after chemotherapy |