Olanzapine for Chemotherapy-Induced Nausea and Vomiting

(FONDO-LOW Trial)

Overseen By Amber Clemmons, PharmD, BCOP, FHOPA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Augusta University

Must be taking: Olanzapine

Must not be taking: Other antipsychotics

Disqualifiers: Allergy to olanzapine, Chronic alcoholism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 4

Duration: 4 days

172 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients who receive a chemotherapy called melphalan are at high risk of having nausea and vomiting. A medication called olanzapine has been shown to decrease nausea and vomiting after chemotherapy. A previous research study found the 10 mg dose of olanzapine (combined with 3 standard medications used routinely to prevent nausea/vomiting) to be effective for patients who received melphalan chemotherapy, but several other studies have shown many patients have a side effect of sleepiness (e.g., sedation) with that dose of the medication. Our study will compare two lower doses of olanzapine (5 mg and 2.5 mg) in combination with the 3 standard medications used to prevent nausea/vomiting in the patients who receive melphalan chemotherapy to determine which dose is effective in preventing nausea and vomiting with the lowest amount of sleepiness side effect.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain antipsychotic medications like risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone at least 30 days before joining. If you're on these medications, you'll need to stop them before participating.

What data supports the effectiveness of the drug Olanzapine for chemotherapy-induced nausea and vomiting?

Research shows that Olanzapine is effective in preventing and treating nausea and vomiting caused by chemotherapy, especially when used with other anti-nausea medications. It works by targeting multiple pathways involved in causing nausea, and its long-lasting effect allows for once-daily dosing. ^{1 2 3 4 5}

Is olanzapine safe for humans?

Olanzapine has been used safely in both children and adults for treating nausea and vomiting caused by chemotherapy, with some reported side effects like sleepiness, high blood sugar, and fatigue. In some studies, no adverse effects were observed, suggesting it is generally safe for human use. ^{1 3 4 6 7}

How is the drug olanzapine different from other treatments for chemotherapy-induced nausea and vomiting?

Olanzapine is unique because it is an antipsychotic drug that targets multiple receptors involved in nausea, allowing it to be effective against chemotherapy-induced nausea and vomiting. It has a long half-life, meaning it can be taken once daily, which is convenient for patients. ^{3 4 5 8 9}

Eligibility Criteria

This trial is for patients undergoing high-dose melphalan chemotherapy, typically used in stem cell transplant and multiple myeloma treatment. Participants should not have a history of sensitivity to olanzapine or other components of the study drugs.

Inclusion Criteria

I have received a stem cell transplant from my own cells.

I have received high-dose melphalan treatment.

Exclusion Criteria

Pregnant

Allergy to olanzapine

Chronic alcoholism

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olanzapine 2.5 mg or 5 mg in combination with standard triplet antiemetic prophylaxis on the day of high-dose melphalan and three days after

4 days

4 visits (in-person)

Follow-up

Participants are monitored for chemotherapy-induced nausea and vomiting (CINV) and sedation outcomes

5 days

Treatment Details

Interventions

• Olanzapine

Trial Overview The study tests two doses of olanzapine (2.5 mg and 5 mg) combined with three standard anti-nausea medications to see which dose effectively prevents nausea/vomiting from melphalan chemo with minimal sleepiness as a side effect.

Participant Groups

Group I: Olanzapine 2.5 mg Experimental Treatment 1 Intervention

Olanzapine 2.5 mg dose to be given on the day of high-dose melphalan and three days after

Group II: Olanzapine 5 mg Active Control 1 Intervention

Olanzapine 5 mg dose to be given on the day of high-dose melphalan and three days after

Olanzapine is already approved in United States, European Union for the following indications:

Approved in United States as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy
• Off-label use for cancer cachexia and anorexia

Approved in European Union as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy

Who Is Running the Clinical Trial?

Augusta University

Lead Sponsor

Trials

219

Recruited

85,900+

Findings from Research

In a phase 3 trial with 380 patients undergoing highly emetogenic chemotherapy, olanzapine significantly reduced nausea compared to placebo, with 74% of patients experiencing no nausea in the first 24 hours versus 45% for placebo.

Olanzapine also improved the complete response rate (no vomiting and no need for rescue medication) significantly, with rates of 86% compared to 65% for placebo, although some patients experienced increased sedation as a side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. Navari, RM., Qin, R., Ruddy, KJ., et al.[2022]

In a study involving patients receiving multiple-day cisplatin chemotherapy, the combination of 5 mg olanzapine with standard antiemetic therapy (triple therapy) showed a significant improvement in preventing nausea and vomiting during the acute phase compared to the triplet group, with a complete response rate of 100% versus 93%.

The quadruple therapy group also demonstrated a longer time to first vomiting episode and a higher overall rate of no vomiting (93.2% vs 80.3%), suggesting that the addition of aprepitant enhances control of chemotherapy-induced nausea and vomiting (CINV) without negatively impacting quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine (5 mg) plus standard triple antiemetic therapy for the prevention of multiple-day cisplatin hemotherapy-induced nausea and vomiting: a prospective randomized controlled study. Gao, J., Zhao, J., Jiang, C., et al.[2022]

In a study of 40 patients with advanced cancer experiencing moderate nausea, olanzapine (10 mg daily for 5 days) significantly reduced nausea scores from 66 to 21 after 24 hours, indicating its effectiveness as an antiemetic.

The treatment was generally well-tolerated, although some patients experienced adverse effects leading to dose reductions, suggesting that future studies could explore lower doses for better safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic use of olanzapine in patients with advanced cancer: results from an open-label multicenter study. Harder, S., Groenvold, M., Isaksen, J., et al.[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 127 cancer patients, olanzapine effectively improved chemotherapy-induced nausea and vomiting (CINV) symptoms, with an 83% improvement rate and a 33% complete response rate, particularly in patients receiving highly emetogenic chemotherapy (HEC).

The study found that olanzapine was generally well-tolerated, with 27% of patients experiencing mild adverse events like somnolence, but no severe adverse events were reported, indicating its safety for use in managing breakthrough CINV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine treatment effectively relieves breakthrough chemotherapy-induced nausea and vomiting: a real-world experience. Uchiike, A., Kono, H., Miura, K., et al.[2023]

In a study of 13 pediatric cancer patients undergoing high and moderate emetogenic chemotherapy, olanzapine was found to be effective, achieving a complete response in 75.6% of chemotherapy cycles.

The use of olanzapine was associated with some adverse effects, including somnolence and hyperglycemia, but overall, it was deemed safe for managing chemotherapy-induced nausea and vomiting, suggesting further research is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Olanzapine for High and Moderate Emetogenic Chemotherapy in Children. Lee, SR., Kim, SM., Oh, MY., et al.[2020]

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 58 patients with acute leukemia undergoing multi-day chemotherapy, the addition of olanzapine to a steroid-sparing antiemetic regimen did not significantly improve the prevention of chemotherapy-induced nausea and vomiting (CINV) compared to a control group.

Both the olanzapine group and the control group experienced similar rates of complete response to CINV and safety events, indicating that olanzapine was well tolerated but did not provide a clear benefit in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine within steroid-sparing antiemetic regimen to prevent chemotherapy-induced nausea and vomiting in patients with acute leukemia receiving multi-day intensive chemotherapy. Hsu, G., Bernhardi, C., Lawson, J., et al.[2023]

Olanzapine has been shown to be more effective than traditional neurokinin-1 receptor antagonists (NK1RA) in preventing nausea and vomiting after highly emetogenic chemotherapy, based on two phase III clinical studies.

In addition to its effectiveness, olanzapine is cost-effective and well-tolerated in cancer patients, with sedation being the main side effect, making it a promising option for managing chemotherapy-induced nausea and vomiting (CINV) and other gastrointestinal symptoms in advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer and chemotherapy-induced nausea and vomiting: a focus on olanzapine. Bosnjak, SM., Dimitrijevic, J., Djordjevic, F.[2018]

References

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

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Olanzapine (5 mg) plus standard triple antiemetic therapy for the prevention of multiple-day cisplatin hemotherapy-induced nausea and vomiting: a prospective randomized controlled study. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Antiemetic use of olanzapine in patients with advanced cancer: results from an open-label multicenter study. [2019]

4. Thailand pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Olanzapine treatment effectively relieves breakthrough chemotherapy-induced nausea and vomiting: a real-world experience. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Olanzapine for High and Moderate Emetogenic Chemotherapy in Children. [2020]

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Olanzapine within steroid-sparing antiemetic regimen to prevent chemotherapy-induced nausea and vomiting in patients with acute leukemia receiving multi-day intensive chemotherapy. [2023]

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

Cancer and chemotherapy-induced nausea and vomiting: a focus on olanzapine. [2018]