Olanzapine With or Without Fosaprepitant for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)in Patients Receiving Highly Emetogenic Chemotherapy (HEC): A Phase III Randomized, Double Blind, Placebo-Controlled Trial

Purpose:

This randomized phase III trial studies how well olanzapine with or without fosaprepitant work in preventing chemotherapy induced nausea and vomiting in cancer patients receiving chemotherapy that causes vomiting. Olanzapine and fosaprepitant dimeglumine may help control nausea and vomiting in patients during chemotherapy. Olanzapine is usually given in combination with other drugs, including fosaprepitant dimeglumine. It is not yet known if olanzapine when given with other drugs, is still effective without using fosaprepitant dimeglumine for controlling nausea and vomiting.

Study summary:

PRIMARY OBJECTIVES: I. To compare between the two study arms the proportion of patients with no nausea for the overall (0-120 hours post-chemotherapy), acute (0-24 hours post-chemotherapy), and delayed periods (24-120 hours post-chemotherapy) for patients receiving highly emetogenic chemotherapy (HEC). SECONDARY OBJECTIVES: I. To compare between the two study arms the complete response (CR) rates (no emetic episodes and no use of rescue medication) in the acute, delayed, and overall periods. II. To compare between the two study arms, the incidences of potential toxicities that have been ascribed to olanzapine. III. To perform an economic evaluation of olanzapine and fosaprepitant dimeglumine (fosaprepitant) versus (vs.) olanzapine in patients receiving HEC (noting that all patients will also receive dexamethasone and a 5HT3 receptor antagonist). IV. To explore the efficacy of olanzapine in chemotherapy cycles two to four, for patients who elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy cycles two to four (continuation phase), by documenting nausea and complete response. V. To explore the safety of olanzapine in chemotherapy cycles two to four, for patients who elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy cycles two to four (continuation phase), by recording any adverse events or drug related toxicities. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive palonosetron hydrochloride intravenously (IV) over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or orally (PO) on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed up periodically.

Criteria:

Inclusion Criteria: - Diagnosis of malignant disease of any stage; (stage I through stage IV) - No prior history of chemotherapy for any malignancy - Scheduled to receive intravenous HEC (highly emetogenic chemotherapy) (either cisplatin-containing regimen or doxorubicin and cyclophosphamide [AC]); cisplatin, given on a single day, at a dose of >= 70 mg/m^2, with or without other chemotherapy agent(s) OR doxorubicin (60 mg/m^2) plus cyclophosphamide (600 mg/m^2) - No nausea or vomiting =< 24 hours prior to registration - Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for women of childbearing potential only * A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) - No known diagnosis of dementia; patients with stable treated brain metastases are eligible to participate - No known history of central nervous system (CNS) disease (e.g. seizure disorder) - No treatment with another antipsychotic agent such as olanzapine, risperidone, quetiapine, clozapine, phenothiazine or butyrophenone =< 30 days prior to registration - No chronic phenothiazine administration as an antipsychotic agent (patients may receive prochlorperazine and other phenothiazines as rescue anti-emetic therapy but not within 24 hours prior to registration) - No use of amifostine within 7 days prior to registration - No radiotherapy within 7 days prior to registration or planned for one week after the current dose of chemotherapy - No use of quinolone antibiotic therapy within 7 days prior to registration - No chronic alcoholism (as determined by the investigator) - No known hypersensitivity to olanzapine - No known uncontrolled cardiac arrhythmia, no known uncontrolled congestive heart failure, or no acute myocardial infarction within the previous six months - No history of uncontrolled diabetes mellitus, i.e., no diabetic ketoacidosis; within 6 months prior to registration; patients are eligible if they have controlled diabetes on diet, oral agents, and/or insulin - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Patients must be able to read and comprehend English; local translation, including verbal translation of patient-reported outcomes (PROs) is not permitted - Serum creatinine =< 2.0 mg/dL =< 120 days prior to registration - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) =< 120 days prior to registration

Study is Available At:

Original ID:

A221602

NCT ID:

NCT03578081

Secondary ID:

NCI-2017-02410

Study Acronym:

Brief Title:

Olanzapine With or Without Fosaprepitant Dimeglumine in Preventing Chemotherapy Induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetog

Official Title:

Olanzapine With or Without Fosaprepitant for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)in Patients Receiving Highly Emetogenic Chemotherapy (HEC): A Phase III Randomized, Double Blind, Placebo-Controlled Trial

ClinicalTrials.gov Link:

https://clinicaltrials.gov/show/NCT03578081

Overall Status:

Active, not recruiting

Study Phase:

Phase 3

Genders:

N/A

Minimum Age:

18 Years

Maximum Age:

N/A

Study Source:

Alliance for Clinical Trials in Oncology

Oversight Authority:

There was an error processing this request

Reasons Why Stopped:

Study Type:

Interventional

Study Design:

Number of Arms:

2

Number of Groups:

0

Total Enrollment:

690

Enrollment Type:

Actual

Data Source: ClinicalTrials.gov

Date Processed: February 01, 2023

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