Cancer-Associated Anorexia, Head and Neck Squamous Cell Carcinoma, Neck Squamous Cell Carcinoma of Unknown Primary
Conditions
Brief summary
This phase II trial compares the effect of adding olanzapine to standard of care symptom management for nausea to standard of care alone in managing an abnormal loss of the appetite for food (anorexia) in patients treated with chemoradiation therapy (CRT) for head and neck cancer. Patients undergoing CRT may experience treatment-related side effects, including pain, nausea, and a discomfort in the ability to speak, swallow and eat. These side effects have been shown to increase weight loss, opiate use and hospitalization. Olanzapine is a drug used to treat certain mental disorders. It is also being studied in the treatment of nausea and vomiting caused by some cancer treatments. It is a type of anti-psychotic and a type of monoamine antagonist. Adding olanzapine to standard of care symptom management to limit nausea may be more effective than standard of care alone in managing anorexia in head and neck cancer patients during CRT.
Detailed description
PRIMARY OBJECTIVE: I. To assess the effect of adding olanzapine to standard symptom management on preventing weight loss during chemoradiation. SECONDARY OBJECTIVES: I. To assess the effect of olanzapine on: * Preventing severe weight loss; * The rate of toxicities-unrelated, possibly- or probably- related to the symptom management regimen (regardless of causality) II, Quality of Life (QOL) scores: * With particular attention to nausea, vomiting, appetite, loss, swallowing, pain; and Special attention to sleep; * Opiate use, hospitalization rate, feeding tube use, chemotherapy delays, and additional olanzapine prescriptions. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard of care symptom management on study per the discretion of the treating institution. ARM II: Starting day 1 of CRT, patients receive olanzapine PO QD for up to 10 weeks after completion of CRT in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care symptom management on study per the discretion of the treating institution. After completion of study treatment, patients are followed up at 5 weeks.
Interventions
OTHERBest Practice
Given standard of care symptom management
DRUGOlanzapine
Given PO
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Diagnosed with biopsy-proven, squamous cell carcinoma of the head and neck, including squamous cell carcinoma of the neck with unknown primary site * Eligible for curative-intent chemoradiation therapy of the head and neck * Patients must be eligible for concurrent systemic therapy (preferably platinum based) as determined by the treating medical oncologist to undergo platinum-based chemotherapy * Ability to swallow and retain oral medication * Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Participants must agree to avoid the following while taking Olanzapine while they are on study: * Taking the drug Symbyax (which already contains olanzapine) * Consuming alcohol * Operating hazardous machinery, including automobiles, until you are reasonably certain that the study drug therapy does not have any bad effects on your mental and physical health * Participant must understand the investigational nature of this study and sign an institutional review board approved written informed consent form prior to receiving any study related procedure
Exclusion criteria
* Eligible for palliative-intent radiation therapy only * Patients with a feeding tube * Regular systemic steroid use * Atypical antipsychotic use * Other dopamine receptor blockers routinely used as anti-emetics (eg. prochlorperazine/compazine and metoclopramide) are allowed to be prescribed as usual care on this study * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes or psychiatric illness/social situations that would limit compliance with study requirements * Known hypersensitivity to olanzapine * Pregnant or nursing female participants * Known history of seizures * Unwilling or unable to follow protocol requirements * Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average change in weight | From baseline to patient lowest weight during chemoradiation therapy (CRT) treatment, assessed up to 5 weeks after last dose of study treatment | Will be summarized by study arm using the mean and standard deviation. A two-sample t-test will be used. All test assumptions will be verified graphically, and transformations or non-parametric approaches will be considered, as appropriate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with severe weight loss | At baseline up to any time point during CRT treatment, assessed up to 5 weeks after last dose of study treatment | Will be defined as \>= 10% body weight loss. Will be summarized by study arm and compared by the Fisher exact test or chi-squared test as appropriate. |
| Incidence of adverse events | Up to 5 weeks after last dose of study treatment | Will be assessed using the Cancer Therapy Evaluation Program National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will be summarized by attribution and grade using frequencies and relative frequencies. Differences in CTCAE rates (grade 2 or higher) will be compared between groups using the Fisher exact Test or chi-Squared test as appropriate. |
| Change in quality of life (QOL) scores | Baseline up to 5 weeks after last dose of study treatment | Will be assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) . The Oral Mucositis Weekly Questionnaire-Head and Neck Cancer will be used to describe the short-term effects of radiation on QOL during treatment. Scores will be assessed by comparing the within-patient change. The treatment effect will be estimated with a generalized linear mixed model, describing the continuous EORTC quality of life outcomes as a function of a random patient effect, and fixed effects for treatment assignment, time, the stratification factor, the treatment assignment and the treatment/time interaction. The magnitude, direction and 95% confidence interval for the adjusted interaction term estimate will be used to describe the effect of olanzapine in improving different QOL domains. An interaction p-value \< 0.05 will be considered statistically significant. |
| Change in Quality of Life | Up to 5 weeks after last dose of study treatment | Will be assessed using the EORTC QLQ-H\&N43 module questionnaire. Mean change from |
| Changes in sleep | Baseline up to 5 weeks after last dose of study treatment | Will be assessed using the Insomnia Severity Index (ISI) score and the ISI category. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test. |
| Opiate use | Up to 5 weeks after last dose of study treatment | Will be defined as proportion of patients requiring opiate prescription during CRT, time to first opiate in days, and total opiate use in morphine milligram equivalents. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test. |
| Hospitalization rate | Up to 5 weeks after last dose of study treatment | Will be defined as proportion of patients requiring inpatient hospital admission for any reason during CRT. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test. |
| Feeding tube use | Up to 5 weeks after last dose of study treatment | Will be defined as the proportion of patients requiring feeding tube insertion during CRT. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test. |
| Chemotherapy delays | Up to 5 weeks after last dose of study treatment | Will be defined as the proportion of patients requiring delays in chemotherapy during CRT. Differences between treatment arms for categorical or binary end points will be compared using the chi-square test or Fisher's exact test as appropriate. Differences between treatment arms for continuous variables will be compared using the Mann-Whitney U test. Differences between treatment arms for time-to-event end points will be compared using Kaplan-Meier estimates and the log-rank test. |
| Additional olanzapine prescriptions | Up to 5 weeks after last dose of study treatment | Will be defined as the proportion of patients prescribed olanzapine for intractable nausea during CRT. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAnurag K Singh
Roswell Park Cancer Institute
Outcome results
None listed