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

Nausea Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02290470
• Other study ID #: Gineolanzapina
• Status: Recruiting
• Phase: Phase 2
• First received: May 22, 2014
• Last updated: November 11, 2014
• Start date: April 2014
• Est. completion date: November 2015

Study information

• Verified date: November 2014
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: Luigi Celio, MD
• Phone: 0039 02 2390
• Email: luigi.celio[@]istitutotumori.mi.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Nausea
• Vomiting

Intervention

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).
• Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine
all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1

Locations

Country	Name	City	State
Italy	Istituto Nazionale dei Tumori	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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)	No
Other	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	Yes
Other	Frequency of rescue anti-emetics	• Frequency of rescue anti-emetics measured by the Nausea and Vomiting Daily Diary/Questionnaire.	up to 5 days	No
Primary	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	No
Secondary	Nausea scores	• Nausea scores measured by the Nausea and Vomiting Daily Diary/Questionnaire.	up to 5 days	No