Olanzapine With or Without Fosaprepitant Dimeglumine in Preventing Chemotherapy Induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetogenic Chemotherapy
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.
Condition
- Malignant Neoplasm
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Supportive Care
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm I (fosaprepitant dimeglumine, olanzapine) |
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, 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. |
|
|
Active Comparator Arm II (placebo, olanzapine) |
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. |
|
More Details
- Status
- Completed
- Sponsor
- Alliance for Clinical Trials in Oncology
Study Contact
Detailed Description
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.