Olanzapine for Appetite Loss in Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Antipsychotics, Cannabinoids, Corticosteroids

Disqualifiers: Diabetes, Renal disease, Uncontrolled infection, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well olanzapine, an antipsychotic medication, can help with appetite loss in individuals with advanced or metastatic cancers such as esophagogastric, hepatopancreaticobiliary, colorectal, or lung cancer. Although typically used for mental health conditions, olanzapine might stimulate appetite and improve quality of life for those experiencing cancer-related weight loss and fatigue. Participants will receive either a low or high dose of olanzapine, or a placebo, to determine which is most effective. The trial seeks individuals who have experienced significant weight loss and are undergoing first-line palliative cancer therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that olanzapine is generally safe for cancer patients who have lost their appetite. One study found that patients taking olanzapine experienced better appetites and improved quality of life. Another study demonstrated that olanzapine helped patients gain weight and reduced nausea, a common side effect of cancer treatment.

While these results are encouraging, some patients might experience side effects. Common side effects include drowsiness and weight gain. Overall, the evidence suggests that olanzapine is safe for managing appetite loss in cancer patients. These findings may reassure those considering joining a trial about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer cachexia?

Olanzapine is unique because it targets appetite loss in cancer patients by acting on neurotransmitters in the brain, potentially improving appetite and reducing nausea. While most treatments for appetite loss in cancer involve nutritional supplements or appetite stimulants like megestrol acetate, olanzapine works differently by modulating neurotransmitter pathways. Researchers are excited about its potential to provide a dual benefit of improving appetite and alleviating nausea, which could enhance the quality of life for cancer patients without the need for multiple medications.

What evidence suggests that olanzapine might be an effective treatment for appetite loss in cancer?

Research has shown that olanzapine can improve appetite in cancer patients. In this trial, participants will receive either a lower dose (2.5 mg), a higher dose (5 mg) of olanzapine, or a placebo. Previous studies reported that patients taking olanzapine experienced a noticeable increase in appetite and felt better overall. One study found that taking 5 mg of olanzapine daily for a short period improved appetite in patients with incurable cancer and severe weight loss, known as cachexia. Additionally, olanzapine has helped cancer patients gain weight. These findings suggest that olanzapine could be a promising option for managing appetite loss in cancer patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Eric Roeland, M.D., FAAHPM, FASCO

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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

Willingness to comply with restrictions on chest/breastfeeding

A negative pregnancy test at baseline must be obtained for individuals capable of childbearing

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Olanzapine

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.

How Is the Trial Designed?

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.

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

Olanzapine, traditionally used for nausea and vomiting in chemotherapy, has shown potential benefits in managing symptoms like anorexia, anxiety, and insomnia in cancer patients, as illustrated by three case reports involving patients with severe symptoms.

While olanzapine can improve quality of life for cancer patients, there are risks associated with its off-label use, such as confusion and hyperammonia, highlighting the need for more research on its safety and efficacy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits and risks of off-label olanzapine use for symptom management in cancer patients-a case report. Dev, R., Fortuno, ES., Amaram-Davila, JS., et al.[2023]

In a retrospective review of 41 cancer patients treated with olanzapine for symptoms beyond chemotherapy-induced nausea and vomiting, 53.7% experienced symptom relief, indicating its potential efficacy in managing various cancer-related symptoms.

Olanzapine was particularly effective for patients with chemotherapy-induced nausea and vomiting that did not respond to standard treatments, with 13 out of 14 patients finding relief, and no treatment-related adverse events were reported, suggesting it is a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Olanzapine for Symptom Relief in Cancer Patients. Nakagawa, N., Suzuki, M.[2023]

In a study involving five cancer patients with severe vomiting unresponsive to standard treatments, olanzapine successfully resolved vomiting completely in 3 patients and improved appetite in those cases.

Olanzapine was well-tolerated with no adverse effects reported, indicating its potential as a safe and effective option for managing nausea and anorexia in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Olanzapine use in cancer patients for refractory vomiting]. Shinjo, T., Okada, M.[2019]

In a phase II clinical trial involving 46 cancer patients undergoing highly emetogenic chemotherapy, olanzapine was found to be effective in controlling breakthrough emesis, with a complete response rate of 60.9% for vomiting, 71.7% for retching, and 50.0% for nausea.

The treatment was well-tolerated, with only mild adverse effects reported, such as dizziness, fatigue, and dyspepsia, indicating that olanzapine is a safe addition to standard antiemetic regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of olanzapine for the treatment of breakthrough chemotherapy induced nausea and vomiting. Chanthawong, S., Subongkot, S., Sookprasert, A.[2018]

In a study of 124 patients with advanced cancers receiving chemotherapy, those treated with low-dose olanzapine showed a significant increase in weight gain (>5%) compared to the placebo group (60% vs. 9%).

Olanzapine also improved appetite and quality of life, with minimal side effects, making it a safe and effective option for managing anorexia in cancer patients undergoing chemotherapy.

NCBI (Pubmed)

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. Sandhya, L., Devi Sreenivasan, N., Goenka, L., et al.[2023]

Olanzapine, while effective for treating nausea in palliative care, can trigger a resurgence of eating disorders, as demonstrated in a case study of a 70-year-old woman with a history of bulimia nervosa.

The patient's bulimia nervosa symptoms improved after reducing the dose of olanzapine, highlighting the need for careful monitoring of eating disorders in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resurgence of Eating Disorders with Olanzapine. Wu, KL., Lorenz, AK., Christensen, KJ., et al.[2020]

In a study of 124 cancer patients receiving selinexor and chemotherapy, prophylactic olanzapine significantly reduced the incidence of nausea and vomiting, while maintaining weight over a 3-month period.

Although olanzapine was well tolerated at a low dose of 2.5 mg daily, it was associated with an increased risk of hyperglycemia, indicating a need for monitoring blood sugar levels in patients.

NCBI (Pubmed)

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. Dev, R., Zhong, LL., Zarifa, A., et al.[2022]

Oral olanzapine significantly increases the likelihood of preventing nausea and vomiting during chemotherapy, improving outcomes from 25% to 50% when added to standard treatment, based on a review of 14 randomized controlled trials involving 1917 participants.

While olanzapine is effective, there is uncertainty regarding its safety, particularly concerning serious adverse events, although it likely increases somnolence and fatigue compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. Sutherland, A., Naessens, K., Plugge, E., et al.[2022]

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