Olanzapine for the Treatment of Chronic Nausea and/or Vomiting, Unrelated to Chemotherapy or Radiation, in Advanced Cancer Patients - A Confirmatory Phase III MNCCTN Trial
Overview
- Phase
- Phase 3
- Status
- Withdrawn
- Sponsor
- Mayo Clinic
- Primary Endpoint
- Change in nausea score
Overview
Brief Summary
This phase III trial compares olanzapine to placebo in decreasing nausea and vomiting in patients with cancer that has spread to other places in the body (advanced). Patients with advanced cancer may experience nausea and/or vomiting that is unrelated to chemotherapy or radiation. Giving olanzapine may help reduce nausea and increase appetite in patients who have advanced cancer.
Detailed Description
PRIMARY OBJECTIVE:
I. To conduct a confirmatory phase III double-blind randomized clinical trial to evaluate the ability of olanzapine to decrease nausea in patients with advanced-cancer associated nausea/vomiting.
SECONDARY OBJECTIVES:
I. To evaluate toxicity associated with olanzapine in patients with advanced-cancer associated nausea/vomiting.
II. To evaluate the effect of olanzapine on appetite, vomiting, sedation, sleep, the use of other antiemetic agents, fatigue, and well-being.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive olanzapine orally (PO) every night on days 1-28.
ARM II: Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age \>= 18 years
- •Histologically or cytologically-confirmed cancer in an advanced incurable stage
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Chronic nausea that has been present for at least one week (daily score \> 5, on a 0-10 visual analogue scale)
- •Serum creatinine \< 2.0 mg/dl =\< 120 days prior to registration
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) values \< 3 times upper limits of normal =\< 120 days prior to registration
- •Negative pregnancy test done =\< 14 days prior to registration, for persons of childbearing potential only
- •Able to provide written informed consent
- •Able to complete questionnaire(s) by themselves or with assistance
Exclusion Criteria
- •Any of the following because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects:
- •Pregnant persons
- •Nursing persons
- •Received chemotherapy or radiation within the prior 14 days (advanced cancer patients receiving hormonal therapy or targeted therapy that does not come with a recommendation for prophylactic anti-emetic therapy are eligible)
- •Receiving treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone for =\< 30 days prior to registration or planned during protocol therapy (patients may have received prochlorperazine and other phenothiazines as prior anti-emetic therapy)
- •Those with concurrent use of ethyol; severe cognitive compromise; concurrent use of amifostine; concurrent use of quinolone antibiotic therapy; known hypersensitivity to olanzapine; or have planned chemotherapy or radiation during the 7 days following study initiation
- •Uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection (including human immunodeficiency virus \[HIV\])
- •Cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
- •Psychiatric illness/social situations that would limit compliance with study requirements
Arms & Interventions
Arm I (olanzapine)
Patients receive olanzapine PO every night on days 1-28.
Intervention: Olanzapine (Drug)
Arm I (olanzapine)
Patients receive olanzapine PO every night on days 1-28.
Intervention: Questionnaire Administration (Other)
Arm II (placebo, olanzapine)
Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
Intervention: Olanzapine (Drug)
Arm II (placebo, olanzapine)
Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
Intervention: Placebo Administration (Drug)
Arm II (placebo, olanzapine)
Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
Intervention: Questionnaire Administration (Other)
Outcomes
Primary Outcomes
Change in nausea score
Time Frame: Baseline to 24 hours of treatment
Evaluated using Visual Analogue Scale. Nausea scores at baseline and after the first two days and the change scores, for the first 2 days, will be summarized using mean (standard deviation) and median (range). The change scores from baseline to the end of the first 2 days will be compared between arms using a two-sample t-test or a Wilcoxon rank sum test as appropriate. The difference in nausea change scores from baseline to 2 days post treatment initiation between the two arms will be estimated along with a 95% confidence interval.
Secondary Outcomes
- Daily nausea and vomiting scores(Up to 28 days)
- Daily episodes of vomiting/retching (number and time)(Up to 28 days)
- Incidence of adverse events with olanzapine(Up to 28 days)
- Utilization of rescue therapy(Up to 28 days)