Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients

Inclusion Criteria:

• Women and men of reproductive potential should agree to use an appropriate method ofbirth control throughout their participation in this study due to the teratogenicpotential of the therapy utilized in this trial. Appropriate methods of birthcontrol include abstinence, oral contraceptives, implantable hormonal contraceptivesor double barrier method (diaphragm plus condom)

• Diagnosis of advanced cancer

• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/orphysician-estimated caloric intake of less than 20 calories/kilogram of body weightper day

• The patient must perceive loss of appetite and/or weight as a problem; and have anappetite score of 4 or worse on the "Please rate your appetite…." question thatrequires a patient response on a 0-10 numeric rating scale

• Not receiving ongoing tube feedings or parenteral nutrition at the time ofregistration

• Not currently using systemic adrenal steroids (with the exception of short-termdexamethasone within 3 days of chemotherapy for control of chemotherapy sideeffects)

• No use of androgens, progesterone analogs, or other appetite stimulants within thepast month

• Patient should not have poorly controlled hypertension or congestive heart failureat registration

• Patient should not have an obstruction of the alimentary canal, malabsorption, orintractable vomiting (defined as vomiting more than 3 times per day over thepreceding week)

• Not currently using olanzapine for another medical condition or had previously usedolanzapine for chronic nausea or for any pre-existing psychotic disorder

• Patient should not have had a previous blood clot at any time in the past

• No history of poorly controlled diabetes

• No symptomatic leptomeningeal disease or known brain metastases as these patientsmay have difficulty taking oral medications

• No history of hypersensitivity to olanzapine or megestrol acetate

• No COVID-19 infection in the past that, in the opinion of the treating physician,had left patients with compromised taste, which has not resolved at the time ofregistration

• Not pregnant and not nursing, because this study involves an investigational agentwhose genotoxic, mutagenic and teratogenic effects on the developing fetus andnewborn are unknown. Therefore, for women of childbearing potential only, a negativeurine or serum pregnancy test done =< 14 days prior to registration is required

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

• Estimated life expectancy of 3 months or longer

• Serum creatinine =< 2.0 mg/dL

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upperlimit of normal (ULN)

• Fasting glucose < 140 mg/dL

• Granulocytes > 1000/hpf

• No treatment with another antipsychotic agent, such as risperidone, quetiapine,clozapine, butyrophenone within 30 days of enrollment

• In order to complete the mandatory patient-completed measures, participants must beable to speak and/or read English or Spanish. Sites seeking to enrollSpanish-speaking patients should have access to Spanish speaking staff on site orthrough the use of a translation service to be able to conduct the informed consentdiscussion in Spanish, and to conduct the weekly phone calls

Exclusion Criteria:

• Psychiatric illness which would prevent the patient from giving informed consent

• Medical condition such as uncontrolled infection (including human immunodeficiencyvirus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in theopinion of the treating physician, would make this protocol unreasonably hazardousfor the patient

• Patients who cannot swallow oral formulations of the agents

• Patients with impaired decision-making capacity (such as with a diagnosis ofdementia or memory loss) are not eligible for this study

• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostatecancer (this exclusion criterion is intended to circumvent any confoundingantineoplastic effects of megestrol acetate)