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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of olanzapine (Zyprexa) to reduce nausea and vomiting in patients undergoing chemotherapy with melphalan, while minimizing sleepiness. It will compare two lower doses of olanzapine (5 mg and 2.5 mg) combined with three standard anti-nausea medications. Suitable candidates include those receiving high-dose melphalan and undergoing autologous stem cell transplantation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

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.

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

Research shows that olanzapine can help reduce nausea and vomiting in people receiving chemotherapy. However, some studies have found that higher doses, such as 10 mg, can cause side effects like drowsiness and dizziness. These are the most common side effects when using this medication for chemotherapy-related nausea.

In studies comparing different doses of olanzapine, both 5 mg and 10 mg effectively managed nausea, with effectiveness not strongly dependent on the dose. This suggests the lower dose might work just as well in some cases. The current trial is testing even lower doses of 5 mg and 2.5 mg to see if they can reduce nausea with fewer side effects.

Overall, olanzapine has been used safely for chemotherapy-induced nausea, but some people may experience sleepiness as a side effect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using olanzapine for chemotherapy-induced nausea and vomiting because it offers a promising alternative to traditional antiemetics like serotonin receptor antagonists and corticosteroids. Unlike these standard treatments, which mainly block serotonin and other neurotransmitters involved in vomiting, olanzapine targets multiple neurotransmitter pathways, including dopamine, which may provide broader relief. Additionally, its potential for effectiveness at lower doses, such as 2.5 mg and 5 mg, could mean fewer side effects, making it a more tolerable option for patients undergoing chemotherapy.

What evidence suggests that this trial's treatments could be effective for chemotherapy-induced nausea and vomiting?

Research shows that olanzapine can help reduce nausea and vomiting caused by chemotherapy. Studies have found that olanzapine is more effective at preventing nausea and stopping vomiting compared to a placebo (a pill with no active medicine). This trial will administer either a 5 mg dose or a 2.5 mg dose of olanzapine to determine if these lower doses can effectively manage symptoms with fewer side effects. Adding a 5 mg dose of olanzapine to standard treatments has been helpful in managing these symptoms, but higher doses can cause side effects like drowsiness. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5465345/

Efficacy of olanzapine for the prophylaxis of chemotherapy ... Compared with other antiemetic agents, olanzapine significantly improved the CR in the delayed and overall phases, but did not enhance the CR in the acute phase ...

2. ar.iiarjournals.org ar.iiarjournals.org/content/45/9/3605

Dose-dependent Efficacy of Olanzapine for Chemotherapy ... Recent studies have used primary outcomes other than CR, as the development of antiemetic agents has reduced the incidence of vomiting and the control of nausea ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1515725

Olanzapine for the Prevention of Chemotherapy-Induced ... Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2804394

Efficacy of Olanzapine in Addition to Standard Triplet ... Findings of this study suggest that adding 5 mg of olanzapine to the standard triplet antiemetic therapy is beneficial for countering nausea and vomiting ...

5. jphcs.biomedcentral.com jphcs.biomedcentral.com/articles/10.1186/s40780-023-00293-y

Olanzapine treatment effectively relieves breakthrough ... Olanzapine treatment prevents chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9689588/

Olanzapine for the Prevention and Treatment of ... The most-reported side effects are drowsiness and dizziness when olanzapine is used to treat nausea and vomiting caused by chemotherapeutic ...

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00233-5/abstract

Overall efficacy and safety of olanzapine 5 mg added to ... The addition of 10 mg olanzapine to the standard triplet antiemetic therapy has shown superiority in controlling chemotherapy-induced nausea ...

8. ejcancer.com ejcancer.com/article/S0959-8049(25)00218-7/fulltext

Olanzapine combined with standard antiemetics for the ... Purpose Prophylactic use of olanzapine significantly improves chemotherapy-induced nausea and vomiting (CINV) in patients receiving single ...