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

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Status and phase: Unknown; Phase 2

Conditions: Vomiting; Nausea

Treatments: Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine; Drug: Olanzapine

Study type: Interventional

Funder types: Other

Identifiers

NCT02290470

Gineolanzapina

Details and patient eligibility

About

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.

Full 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.

Enrollment: 81 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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81 participants in 3 patient groups

olanzapine Days 1-3

Experimental group

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)

Treatment:

Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine

Drug: Olanzapine

olanzapine+Dexamethasone d 1-3

Experimental group

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)

Treatment:

Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine

Drug: Olanzapine

dexamethasone days 1-3

Active Comparator group

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

Treatment:

Drug: Palonosetron, Dexamethasone, Carboplatin, Paclitaxel, Olanzapine

Drug: Olanzapine