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

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

Sponsors

Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Source Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Brief 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.

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.

Overall Status Unknown status
Start Date April 2014
Completion Date November 2015
Primary Completion Date November 2015
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Complete Protection days 2-5 post-chemotherapy
Secondary Outcome
Measure Time Frame
Nausea scores up to 5 days
Enrollment 81
Condition
Intervention

Intervention type: Drug

Intervention name: Olanzapine

Description: 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).

Intervention type: Drug

Intervention name: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine

Description: all patients enrolled in the study will receive Palonosetron, Dexamethasone, Carboplatin, Paclitaxel and olanzapine On day 1

Eligibility

Criteria:

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.

Gender: Female

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Luigi Celio, MD Luigi Celio, MD Luigi Celio, MD
0039 02 2390 0039 02 2390 0039 02 2390
2597 2597 2597
[email protected] [email protected] [email protected]
Overall Contact

Last name: Luigi Celio, MD

Phone: 0039 02 2390

Phone ext: 2597

Email: [email protected]

Location
facility status investigator
Istituto Nazionale dei Tumori Recruiting Luigi Celio Principal Investigator
Location Countries

Italy

Verification Date

November 2014

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: olanzapine Days 1-3

Arm group type: Experimental

Description: 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)

Arm group label: olanzapine+Dexamethasone d 1-3

Arm group type: Experimental

Description: 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)

Arm group label: dexamethasone days 1-3

Arm group type: Active Comparator

Description: 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

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Supportive Care

Masking: None (Open Label)

Source: ClinicalTrials.gov