Using olanzapine to help cancer patients regain appetite and manage weight loss

Inclusion Criteria:

* Willingness to provide written informed consent
* Individuals \>= 18 years of age
* Histologically confirmed advanced local or metastatic esophogastric, hepatopancreaticobiliary, colorectal, or lung cancer diagnosis within 12 weeks of screening
* Patients with weight loss as defined by international consensus criteria (documented or patient-reported):

  * ≥ 5% weight loss over the past 6 months
  * ≥ 2% weight loss with body mass index (BMI) \<20 kg/m\^2 or sarcopenia
* Planned or ongoing first-line palliative antineoplastic therapy (cytotoxic chemotherapy, targeted therapy, immunotherapy, combinations) with or without radiation therapy and have not started the second cycle of first-line palliative antineoplastic therapy. Patients may have received adjuvant antineoplastic therapy at least 6 months prior to screening
* Able to ambulate independently with or without assistive devices (e.g., cane, walker)
* In the case of brain metastases, the individual must be asymptomatic or previously treated with a full cycle of therapy with recovery from any acute effects of radiation therapy or surgery before screening. Such individuals must have discontinued corticosteroid treatment and be neurologically stable for at least 4 weeks before screening
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Able and willing to discontinue the use of any drug or over-the-counter (OTC) product that may interact with the study drug (within a period sufficient for wash-out per the principal investigators \[PI's\] discretion) and thereafter while on the study
* Willingness to comply with restrictions on chest/breastfeeding
* Individuals capable of childbearing and contributing viable sperm must be willing to comply with contraception requirements and not donate ova or sperm while on the study and for 1 month after that
* A negative pregnancy test at baseline (BL) must be obtained for individuals capable of childbearing

Exclusion Criteria:

* Plan for, or history of (within 30 days of enrollment), the use of an antipsychotic drug, including, but not limited to, risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone. This limitation does not include prochlorperazine and other phenothiazines as antiemetic therapy. The use of antipsychotics concurrent with protocol therapy will not be allowed
* Current use of medications or supplements with the goal of enhancing appetite within ≥14 days, including:

  * megestrol acetate
  * cannabinoids (including, but not limited to dronabinol, medical cannabis, over the counter \[OTC\] cannabinoid products), and/or
  * Corticosteroids (defined as ≥ 5mg of prednisone \[or equivalent per day\]), except for standard-of-care chemotherapy-induced nausea and vomiting prophylaxis
* Known history of poorly controlled diabetes, defined as fasting morning blood sugars ≥300 mg/dL or recent hemoglobin A1≥ 8. Individuals with diabetes will undergo hemoglobin A1c (HbA1c) blood testing if they do not have HbA1c results 12 weeks prior to enrollment
* Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days before signing consent:

  * Total bilirubin ≥5x upper limit of normal (ULN), aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SPGT\]) ≥5X ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma, or hepatic metastases)
  * Primary investigator (PI) discretion will determine continued eligibility after randomization occurs in the event the liver function test results are above the proposed ULN
  * Renal disease requiring dialysis or calculated glomerular filtration rate (GFR) ≤ 30 mL/minute/1.73 m\^2 as calculated by the modification of diet in renal disease (MDRD) equation
* Tube feeding or parenteral nutrition at the time of screening
* Any condition that may negatively impact oral absorption of the study drug (including, but not limited to dysphagia, mucositis, gastrectomy, colitis, bowel obstruction, high output ileostomy) or any plan to undergo an intervention that will render such a condition
* Recurrent ascites unresponsive to medical interventions and requires therapeutic paracentesis
* Uncontrolled symptoms at randomization make the individual unsuitable for the study in the judgment of the PI. If uncontrolled symptoms can be effectively palliated for ≥1 week prior, enrollment may be considered at the discretion of the PI
* Uncontrolled infection, including coronavirus disease 2019 (COVID-19), at time of randomization. Individuals with the uncontrolled infection will not be eligible as the symptomology of infection may obscure the outcomes of this study
* Other medical or psychiatric condition, including recent (within 1 year) or active suicidal ideation/behavior or laboratory abnormality, may increase the risk of study participation or, in the PI's judgment, makes the participant inappropriate for the study