Olanzapine for Appetite Loss in Cancer

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}

Research Team

Eric Roeland, M.D., FAAHPM, FASCO

Principal Investigator

OHSU Knight Cancer Institute

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.

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Dr. Shivaani Kummar

OHSU Knight Cancer Institute

Chief Executive Officer

MD, FACP

Dr. Gordon Mills

OHSU Knight Cancer Institute

Chief Medical Officer since 2022

MD, PhD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

John Hunter

Oregon Health and Science University

Chief Medical Officer since 2024

MD, specific details unavailable

Ann Madden Rice

Oregon Health and Science University

Chief Executive Officer

FACHE certification, extensive leadership experience in academic health centers

Findings from Research

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]

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 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]

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 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 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]

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]

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]

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]

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

[Olanzapine use in cancer patients for refractory vomiting]. [2019]

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]

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]

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

Effectiveness of olanzapine for the treatment of breakthrough chemotherapy induced nausea and vomiting. [2018]

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

Efficacy of Olanzapine for Symptom Relief in Cancer Patients. [2023]

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

Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. [2022]

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

Resurgence of Eating Disorders with Olanzapine. [2020]