Olanzapine for Appetite Loss in Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Eric Roeland, M.D., FAAHPM, FASCO

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Antipsychotics, Cannabinoids, Corticosteroids

Disqualifiers: Diabetes, Renal disease, Uncontrolled infection, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well olanzapine works in managing cancer cachexia in patients experiencing esophagogastric, hepatopancreaticobiliary, colorectal, or lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) -associated appetite loss while receiving non-curative cancer therapy. Loss of appetite ("anorexia") in the setting of cancer is a key feature of "cachexia," a syndrome associated with loss of weight and muscle as well as weakness and fatigue. Olanzapine is a drug that targets key neurotransmitters (a type of molecule in the central nervous system that transmits messages to the rest of the body) that may stimulate appetite, restore caloric intake, minimize weight loss, and improve quality of life (QOL).

Will I have to stop taking my current medications?

The trial requires participants to stop using any drugs or over-the-counter products that may interact with the study drug, as determined by the investigator. Additionally, you cannot use certain medications or supplements aimed at enhancing appetite within 14 days before the trial.

What data supports the effectiveness of the drug Olanzapine for appetite loss in cancer patients?

Research shows that Olanzapine can help improve appetite and weight gain in cancer patients undergoing chemotherapy, as well as manage symptoms like nausea and vomiting, which are often linked to appetite loss. ^{1 2 3 4 5}

Is olanzapine safe for use in cancer patients?

Olanzapine has been used in cancer patients to manage symptoms like nausea, vomiting, and appetite loss, with studies reporting no adverse effects in these cases. It is generally considered safe for symptom management in cancer patients. ^{1 2 3 4 6}

How does the drug olanzapine differ from other treatments for appetite loss in cancer patients?

Olanzapine is unique because it is originally an antipsychotic medication that affects multiple brain receptors, and it is being used off-label to help increase appetite and manage symptoms like nausea and vomiting in cancer patients. Unlike standard treatments, it has the added benefit of potentially improving both appetite and weight gain, which are critical for patients undergoing chemotherapy. ^{1 2 4 7 8}

Eligibility Criteria

This trial is for adults with advanced, incurable solid tumors like gastric, liver or lung cancer who are experiencing appetite loss. They must be undergoing non-curative cancer therapy and have an ECOG performance status of 0-2. Participants should not be pregnant, must agree to use contraception, and cannot have certain medical conditions or be on conflicting medications.

Inclusion Criteria

Willingness to provide written informed consent. For decisional impairment or conditions that render the individual unable to independently provide consent, a legally authorized representative must be available or designated in conjunction with the study consent process

Individuals >= 18 years of age of all races, ethnicities, sexual orientations, gender identities, and abilities may be screened for enrollment without bias

Willingness to comply with restrictions on chest/breastfeeding

Exclusion Criteria

Plan for, or history of (within 30 days of registration), 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

Known history of poorly controlled diabetes, defined as fasting morning blood sugars > 300 mg/dL or recent hemoglobin A1c >= 8

Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days before signing consent: Total bilirubin > upper limit of normal (ULN), aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) > 2.5 ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma, or hepatic metastases). Serum creatinine > 2.0 mg/dL 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. NOTE: Investigator discretion will determine continued eligibility after randomization occurs in the event the liver function test results are greater than (>) the proposed upper limit of normal. Tube feeding or parenteral nutrition at the time of screening

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olanzapine or placebo nightly for 12 weeks to manage cancer cachexia

12 weeks

Monthly visits for blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Open-label extension (optional)

Participants may opt into an additional 12 weeks of treatment with olanzapine

12 weeks

Treatment Details

Interventions

• Olanzapine (Antipsychotic)

Trial Overview The trial is testing if olanzapine can help manage appetite loss in patients with advanced cancers. It involves comparing the effects of olanzapine against a placebo while also collecting biospecimens and using questionnaires to assess quality of life.

Participant Groups

Group I: Arm II Experimental Treatment 2 Interventions

Patients receive a higher dose (5 mg) of olanzapine PO nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients undergo an optional baseline CT scan and collections of monthly blood samples on study.

Group II: Arm I (olanzapine, optional biospecimen collection) Experimental Treatment 2 Interventions

Patients receive a lower (2.5mg) dose of olanzapine orally (PO) nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients can choose to undergo computed tomography (CT) scan at baseline and monthly blood sample collections on study.

Group III: Arm III Placebo Group 2 Interventions

ARM III: Patients receive placebo PO nightly for 12 weeks in the absence of unacceptable toxicity. Patients may choose to enroll in an additional 12 weeks of treatment. Patients undergo CT scan and monthly collection of blood samples on study.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

OHSU Knight Cancer Institute Portland, OR

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute Lead Sponsor

National Cancer Institute (NCI) Collaborator

Oregon Health and Science University Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer. [2023] Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy.

2. Japan pubmed.ncbi.nlm.nih.gov

[Olanzapine use in cancer patients for refractory vomiting]. [2019] Recent investigations suggest the efficacy of olanzapine in cancer patients with intractable vomiting or chemotherapy-induced nausea. Olanzapine,indicated for schizophrenia in Japan, has an affinity for multiple neurotransmitter receptors including dopaminergic, serotonergic, histaminergic, adrenergic and muscarinic receptors. This pharmacological activity thus has a potential role in the treatment of nausea and vomiting. In the present study, olanzapine was given to five cancer patients with refractory vomiting to standard medications. In 3 cases, olanzapine resolved vomiting completely and also improved anorexia, In 2 cases, vomiting was controlled for a limited period. No adverse effect was observed. These results suggest olanzapine is a useful agent for the management of both vomiting and anorexia.

3. United States pubmed.ncbi.nlm.nih.gov

Supportive care for the prevention of nausea, vomiting and anorexia in a phase 1B study of selinexor in advanced cancer patients: an exploratory study. [2022] Clinical observations of cancer patients treated with selinexor have reported high incidence of nausea and anorexia. The study objective was to investigate the adoption of prophylactic olanzapine for the prevention of nausea, vomiting and anorexia in cancer patients receiving selinexor and standard chemotherapy.

4. China pubmed.ncbi.nlm.nih.gov

Benefits and risks of off-label olanzapine use for symptom management in cancer patients-a case report. [2023] Cancer patients often experience symptoms such as anorexia, anxiety and insomnia, which can impact their quality of life. Randomized placebo-controlled trials support prophylactic use of olanzapine for the prevention of nausea and vomiting due to moderate and high-emetic risk chemotherapy. In the setting of palliative care, olanzapine is increasingly utilized as an off-label treatment of symptoms including anorexia-cachexia, anxiety, and insomnia. The following case reports will highlight the potential benefits and risks of off-label olanzapine use for symptom management in cancer patients.

5. Thailand pubmed.ncbi.nlm.nih.gov

Effectiveness of olanzapine for the treatment of breakthrough chemotherapy induced nausea and vomiting. [2018] To evaluate safety and efficacy of olanzapine for breakthrough emesis in addition to standard antiemetic regimen in cancer patients receiving highly emetogenic chemotherapy.

6. England pubmed.ncbi.nlm.nih.gov

Efficacy of Olanzapine for Symptom Relief in Cancer Patients. [2023] Olanzapine is an atypical antipsychotic and is widely used for prophylaxis of chemotherapy-induced nausea and vomiting in cancer patients. Previous studies have suggested its potential efficacy for the relief of various symptoms in cancer patients, especially gastrointestinal and psychiatric symptoms. We retrospectively reviewed the prescription of olanzapine to cancer patients at our hospital. Between 2008 and 2020, olanzapine was prescribed to 41 patients for relief of symptoms associated with cancer other than prophylaxis of chemotherapy-induced nausea and vomiting. Of those patients, symptom relief was seen in 53.7%. Notably, olanzapine was effective in 13 of 14 patients with chemotherapy-induced nausea and vomiting refractory to guideline-recommended prophylaxis. Of 16 patients in whom this symptom was not relieved by olanzapine, 13 (81.3%) continued taking olanzapine even after it was judged ineffective. No treatment-related adverse events were seen in this study. Our observation implies good efficacy of olanzapine for refractory chemotherapy-induced nausea and vomiting and a tendency to continue olanzapine even in those for whom it was ineffective.

7. England pubmed.ncbi.nlm.nih.gov

Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. [2022] Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or radiotherapy, or whilst in the palliative phase of illness.

8. United States pubmed.ncbi.nlm.nih.gov

Resurgence of Eating Disorders with Olanzapine. [2020] Olanzapine is commonly utilized in palliative care for the treatment of nausea, and a known side effect of olanzapine is increased appetite. Olanzapine is also known to cause re-emergence of eating disorders (EDs) in patients utilizing olanzapine for its antipsychotic effects. It is unclear to what extent this may also occur in patients with serious/life-limiting illness.