Clinical trial NCT02290470: Olanzapine Against Delayed Nausea and Vomiting in Women Receiving Carboplatin Plus Paclitaxel
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Nausea
Vomiting
Keywords: Nausea
Vomiting
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2014-11-14
Enrollment: 81
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Complete Protection
timeFrame: days 2-5 post-chemotherapy
Secondary outcomes:
measure: Nausea scores
timeFrame: up to 5 days
Other outcomes:
measure: Proportion of patients achieving Complete Response
timeFrame: up to 5 days
measure: Impact of nausea and vomiting on daily life activities
timeFrame: day 1 (pre-chemotherapy) and day 6 (post-chemotherapy)
measure: Incidence of potential toxicities related to olanzapine
timeFrame: up to 5 days
measure: Frequency of rescue anti-emetics
timeFrame: up to 5 days
Locations:
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori
Study officials:
affiliation: Istituto tumori
name: Luigi Celio, MD
role: STUDY_CHAIR
affiliation: Istituto tumori
name: Domenica Lorusso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Tumori
name: Gabriella Saibene, PharmD
role: PRINCIPAL_INVESTIGATOR
References: