Olanzapine With or Without Fosaprepitant Dimeglumine in Preventing Chemotherapy Induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetogenic Chemotherapy
- Conditions
- Malignant Neoplasm
- Interventions
- Registration Number
- NCT03578081
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 690
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Diagnosis of malignant disease of any stage; (stage I through stage IV)
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No prior history of chemotherapy for any malignancy
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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)
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No nausea or vomiting =< 24 hours prior to registration
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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)
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No known diagnosis of dementia; patients with stable treated brain metastases are eligible to participate
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No known history of central nervous system (CNS) disease (e.g. seizure disorder)
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No treatment with another antipsychotic agent such as olanzapine, risperidone, quetiapine, clozapine, phenothiazine or butyrophenone =< 30 days prior to registration
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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)
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No use of amifostine within 7 days prior to registration
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No radiotherapy within 7 days prior to registration or planned for one week after the current dose of chemotherapy
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No use of quinolone antibiotic therapy within 7 days prior to registration
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No chronic alcoholism (as determined by the investigator)
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No known hypersensitivity to olanzapine
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No known uncontrolled cardiac arrhythmia, no known uncontrolled congestive heart failure, or no acute myocardial infarction within the previous six months
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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
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Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
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Patients must be able to read and comprehend English; local translation, including verbal translation of patient-reported outcomes (PROs) is not permitted
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Serum creatinine =< 2.0 mg/dL =< 120 days prior to registration
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) =< 120 days prior to registration
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (fosaprepitant dimeglumine, olanzapine) Palonosetron Hydrochloride 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. Arm I (fosaprepitant dimeglumine, olanzapine) Ondansetron Hydrochloride 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. Arm II (placebo, olanzapine) Palonosetron Hydrochloride 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. Arm II (placebo, olanzapine) Ondansetron Hydrochloride 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. Arm I (fosaprepitant dimeglumine, olanzapine) Fosaprepitant Dimeglumine 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. Arm II (placebo, olanzapine) Placebo 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. Arm I (fosaprepitant dimeglumine, olanzapine) Dexamethasone 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. Arm I (fosaprepitant dimeglumine, olanzapine) 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. Arm II (placebo, olanzapine) Dexamethasone 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. Arm II (placebo, olanzapine) 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.
- Primary Outcome Measures
Name Time Method No Nausea Rate Defined as a Response of 0 in the Nausea Item of Nausea and Vomiting Daily Diary/Questionnaire in the Overall (0-120 Hours), Acute (0-24 Hours), and Delayed (24-120 Hours) Periods Up to 120 hours The specific measure will be based on the proportion of patients with a value of 0, as measured by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Questionnaire. A modified intent-to-treat principle will be applied for statistical analysis of efficacy in evaluable patients. The proportions of patients with no nausea during the overall, the acute, and the delayed period will be summarized by treatment arm. They will be tested in a sequential manner, using a Simes gatekeeping procedure to maintain the overall significance level at the specified by the Lan-DeMets family of alpha spending function. The difference in no nausea proportions between arms will be estimated along with a one-sided 95% confidence interval. The tests and the confidence intervals will be constructed using normal approximation of the binomial distribution adjusted for the non-inferiority margin.
- Secondary Outcome Measures
Name Time Method Potential Toxicities as Ascribed to Olanzapine as Measured by the Nausea and Vomiting Daily Diary/Questionnaire Up to 120 hours Potential toxicities includes nausea, undesired sedation, and undesired appetite, measured by three individual items ( nausea, undesired sedation, undesired appetite) of the Nausea and Vomiting Daily Dairy/Questionnaire(scale 0-10, 0 is no symptoms, 10 is worst symptoms). Incidences of toxicities will be summarized by type and by treatment arm. Incidences of toxicities will be compared between arms using a Chi-squared test or the Fisher's exact test as appropriate. In addition, undesired sedation and appetite increase as collected in the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed by repeated measures analyses including descriptive statistics, graphical approaches, and growth curve models to account for the factor of day and time trend.
Total Frequency of Rescue Medication as Measured by the Nausea and Vomiting Daily Diary/Questionnaire Over 5 Days per each of the 4 cycles The specific measure will be based on the single item : number of extra nausea/vomiting pills taken (None, One , Twice, More than twice) of the Nausea and Vomiting Daily Diary/Questionnaire.
Complete Response (CR) (no Emetic Episodes and no Use of Rescue Medication) During the Acute, Delayed and the Overall Periods as Measured by the Nausea and Vomiting Daily Diary/Questionnaire Up to 120 hours The specific measure will be based on the proportion of patients who answered "None" to both questions concerning Vomiting episode(None, Once, Twice, More than twice) and number of extra nausea/vomiting pills taken (None, One, Two, More than two) in the Nausea and Vomiting Daily Diary/Questionnaire. The CR rate for the overall, the acute, and the delayed period will be summarized by treatment arm and will be compared using a Chi-squared test. The difference in CR rates between arms will be estimated along with a 95% confidence interval.
Average Nausea Scores (0-10) Repeatedly Measured by the Nausea and Vomiting Daily Diary/Questionnaire Up to 1 year The specific measure will be based on the by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Nausea and Vomiting Daily Diary/Questionnaire. Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire will be analyzed using the repeated measures analyses and growth curve models as described above for undesired sedation and increase in appetite.
Trial Locations
- Locations (565)
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Fairbanks Memorial Hospital
🇺🇸Fairbanks, Alaska, United States
Kingman Regional Medical Center
🇺🇸Kingman, Arizona, United States
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
🇺🇸Jonesboro, Arkansas, United States
PCR Oncology
🇺🇸Arroyo Grande, California, United States
Epic Care-Dublin
🇺🇸Dublin, California, United States
Bay Area Breast Surgeons Inc
🇺🇸Emeryville, California, United States
Scroll for more (555 remaining)University of Alabama at Birmingham Cancer Center🇺🇸Birmingham, Alabama, United States