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

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

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.

Study Overview

• Status: Unknown
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: Olanzapine; Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine

Detailed Description

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:

1. 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.
2. To determine the incidences of potential toxicities ascribed to olanzapine.
3. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 81
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Luigi Celio, MD; Phone Number: 2597 0039 02 2390; Email: luigi.celio@istitutotumori.mi.it
• Study Contact Backup: Name: trialcenter trialcenter; Phone Number: 3824 0039 02 2390; Email: trialcenter@istitutotumori.mi.it

Study Locations

• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Istituto Nazionale dei Tumori
    • Principal Investigator: Luigi Celio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: olanzapine Days 1-3; 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; 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).; Other Names: Dexamethasone; Carboplatin; Paclitaxel; Palonosetron; Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine; all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1
Experimental: olanzapine+Dexamethasone d 1-3; 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; 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).; Other Names: Dexamethasone; Carboplatin; Paclitaxel; Palonosetron; Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine; all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1
Active Comparator: dexamethasone days 1-3; 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; 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).; Other Names: Dexamethasone; Carboplatin; Paclitaxel; Palonosetron; Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine; all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving Complete Response	• Proportion of patients achieving Complete Response, defined as no emetic episodes and no use of rescue anti-emetics measured by the Nausea and Vomiting Daily Diary/Questionnaire.	up to 5 days
Impact of nausea and vomiting on daily life activities	• Impact of nausea and vomiting on daily life activities as measured by the Functional Living Index-Emesis Questionnaire.	day 1 (pre-chemotherapy) and day 6 (post-chemotherapy)
Incidence of potential toxicities related to olanzapine	• Incidence of potential toxicities related to olanzapine as measured by the Nausea and Vomiting Daily Diary/Questionnaire. [Time frame: ] [Designated as safety issue: Yes]	up to 5 days
Frequency of rescue anti-emetics	• Frequency of rescue anti-emetics measured by the Nausea and Vomiting Daily Diary/Questionnaire.	up to 5 days

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Study Chair: Luigi Celio, MD, Istituto Tumori; Principal Investigator: Domenica Lorusso, MD, Istituto Tumori; Principal Investigator: Gabriella Saibene, PharmD, Istituto Tumori

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): November 1, 2015
• Study Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: May 22, 2014
• First Submitted That Met QC Criteria: November 11, 2014
• First Posted (Estimate): November 14, 2014

Study Record Updates

• Last Update Posted (Estimate): November 14, 2014
• Last Update Submitted That Met QC Criteria: November 11, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Nausea; Vomiting
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Antineoplastic Agents, Phytogenic; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Carboplatin; Paclitaxel; Olanzapine; Palonosetron; Albumin-Bound Paclitaxel
• Other Study ID Numbers: Gineolanzapina