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Trial record 1 of 1 for:    A221602
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Olanzapine With or Without Fosaprepitant Dimeglumine in Preventing Chemotherapy Induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetogenic Chemotherapy

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ClinicalTrials.gov Identifier: NCT03578081
Recruitment Status : Recruiting
First Posted : July 5, 2018
Last Update Posted : March 6, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE June 25, 2018
First Posted Date  ICMJE July 5, 2018
Last Update Posted Date March 6, 2020
Actual Study Start Date  ICMJE October 15, 2018
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2018)
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 [ Time Frame: Up to 120 hours ]
A modified intent-to-treat principle will be applied for statistical analysis of efficacy in evaluable patients. Evaluable patients are defined as all patients meeting the eligibility criteria who did not cancel prior to receiving treatment and had no major violations. 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
  • 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 [ Time Frame: 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.
  • Potential toxicities as ascribed to olanzapine as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ]
    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.
  • Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: 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.
  • Frequency of rescue medication as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ]
    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. The proportion of patients taking any rescue medication as reported in the Nausea and Vomiting Daily Diary/Questionnaire will be summarized by treatment arm and will be compared between arms using a Chi-squared test or the Fisher's exact test as appropriate. In addition, the number of pills taken will be analyzed using the repeated measures analyses and growth curve models.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2018)
  • 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 [ Time Frame: Up to 120 hours ]
    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.
  • Potential toxicities as ascribed to olanzapine as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ]
    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.
  • Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ]
    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.
  • Frequency of rescue medication as measured by the Nausea and Vomiting Daily Diary/Questionnaire [ Time Frame: Up to 1 year ]
    The proportion of patients taking any rescue medication as reported in the Nausea and Vomiting Daily Diary/Questionnaire will be summarized by treatment arm and will be compared between arms using a Chi-squared test or the Fisher's exact test as appropriate. In addition, the number of pills taken will be analyzed using the repeated measures analyses and growth curve models.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Olanzapine With or Without Fosaprepitant Dimeglumine in Preventing Chemotherapy Induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetogenic Chemotherapy
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Condition  ICMJE Malignant Neoplasm
Intervention  ICMJE
  • Drug: Palonosetron Hydrochloride
    Given IV
  • Drug: Ondansetron Hydrochloride
    Given IV or PO
  • Drug: Dexamethasone
    Given PO
  • Drug: Fosaprepitant Dimeglumine
    Given IV
  • Drug: Olanzapine
    Given PO
  • Other: Placebo
    Given IV
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Palonosetron Hydrochloride
    • Drug: Ondansetron Hydrochloride
    • Drug: Dexamethasone
    • Drug: Fosaprepitant Dimeglumine
    • Drug: Olanzapine
  • 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.
    Interventions:
    • Drug: Palonosetron Hydrochloride
    • Drug: Ondansetron Hydrochloride
    • Drug: Dexamethasone
    • Drug: Olanzapine
    • Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 25, 2018)
690
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rudolph Navari, MD, PhD, FACP 205-975-2833 rnavari@uabmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03578081
Other Study ID Numbers  ICMJE A221602
NCI-2017-02410 ( Registry Identifier: NCI Clinical Trial Reporting Program )
UG1CA189823 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Rudolph Navari, MD, PhD, FACP University of Alabama at Birmingham
PRS Account Alliance for Clinical Trials in Oncology
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP