Olanzapine vs Dexamethasone for Chemo-Related Nausea and Vomiting

Overseen By Kelly Wurzler, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Guthrie Clinic

Must not be taking: Glucocorticoids, Antiemetics

Disqualifiers: Nausea, Radiation, Brain metastases, others

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

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

Compensation: Varies

Number of Visits: 2

104 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to compare two drugs that are routinely used as standard of care for treating nausea and vomiting caused by chemotherapy. This study aims to see if the drug olanzapine is as good as the steroid drug dexamethasone for preventing nausea and vomiting after chemotherapy. Both drugs are listed as appropriate treatment options in the most recent version of National Comprehensive Cancer Network guidelines on Antiemesis.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medication that has antiemetic properties (medications that prevent nausea and vomiting) and you cannot be on glucocorticoid therapy (a type of steroid treatment).

What data supports the effectiveness of the drug Olanzapine and Dexamethasone for chemo-related nausea and vomiting?

Research shows that olanzapine is effective in preventing chemotherapy-induced nausea and vomiting, and dexamethasone has been shown to reduce vomiting in patients who did not respond to other treatments. Combining these drugs may help manage nausea and vomiting in cancer patients undergoing chemotherapy. ^{1 2 3 4 5}

Is the combination of olanzapine and dexamethasone safe for preventing chemotherapy-related nausea and vomiting?

Olanzapine and dexamethasone have been studied for safety in preventing nausea and vomiting during chemotherapy. Olanzapine can cause drowsiness, but no major safety issues were reported in studies. Dexamethasone is known for side effects, but its safety in combination with other drugs has been widely evaluated. ^{6 7 8 9 10}

How is the drug combination of Olanzapine and Dexamethasone unique for treating chemo-related nausea and vomiting?

The combination of Olanzapine and Dexamethasone is unique because it adds Olanzapine, an antipsychotic with anti-nausea properties, to standard antiemetic regimens, potentially enhancing effectiveness against chemotherapy-induced nausea and vomiting, especially in highly emetogenic treatments like those involving cisplatin. ^{6 7 9 10 11}

Research Team

Zane Waite, PharmD, BCOP

Principal Investigator

The Guthrie Clinic

Eligibility Criteria

This trial is for adults with cancer who are about to start a highly nausea-inducing chemotherapy, as per guidelines. They must be in good physical condition (ECOG score 0 or 1) and have normal kidney, liver, and blood function. It's not for those already on steroids, receiving radiation close to chemo time, with brain metastases, pre-chemo nausea/vomiting, steroid contraindications or taking anti-nausea meds.

Inclusion Criteria

I am fully active or can carry out light work.

My blood counts are within normal ranges.

My liver is working well.

Exclusion Criteria

I am scheduled for radiation soon or at the same time as chemotherapy.

I am taking medication that helps prevent vomiting.

My cancer has spread to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Cycle 1

Participants receive either dexamethasone or olanzapine for the first cycle of chemotherapy

1 week

1 visit (in-person), 2 follow-up calls

Treatment Cycle 2

Participants switch to the other drug (olanzapine or dexamethasone) for the second cycle of chemotherapy

1 week

1 visit (in-person), 2 follow-up calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexamethasone
• Olanzapine

Trial Overview The study compares Olanzapine (an antipsychotic drug) with Dexamethasone (a steroid), both approved treatments for preventing chemotherapy-induced nausea and vomiting. The goal is to determine if Olanzapine can be an alternative to the standard Dexamethasone therapy without compromising effectiveness.

Participant Groups

Group I: OLA then crossover to DEX Experimental Treatment 2 Interventions

OLA group: olanzapine (Zyprexa) 10 mg oral each night after chemotherapy cycle 1 on days 1-4 after HEC (or days 1-3 after MEC). DEX group: dexamethasone (Decadron) 8 mg oral daily after chemotherapy cycle 2 on days 2-4 after HEC (or days 2-3 after MEC)

Group II: DEX then crossover to OLA Active Control 2 Interventions

DEX group: dexamethasone (Decadron) 8 mg oral daily after chemotherapy cycle 1 on days 2-4 after HEC (or days 2-3 after MEC) OLA group: olanzapine (Zyprexa) 10 mg oral each night after chemotherapy cycle 2 on days 1-4 after HEC (or days 1-3 after MEC).

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

The Guthrie Clinic

Lead Sponsor

Trials

27

Recruited

1,700+

Findings from Research

In a study of 108 patients receiving BEP chemotherapy, switching from a steroid-containing antiemetic protocol to a steroid-sparing protocol using olanzapine resulted in a significant reduction in febrile neutropenia (FN) incidence from 22% to 7.5%.

While the overall incidence of neutropenia was similar between the two groups, the steroid-sparing protocol was associated with a higher rate of severe neutropenia, indicating that while it may reduce FN-related hospital admissions, it could also lead to more severe cases of neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neutropenic sepsis rates in patients receiving bleomycin, etoposide and cisplatin chemotherapy using olanzapine and reduced doses of dexamethasone compared to a standard antiemetic regimen. Gjafa, E., Ng, K., Grunewald, T., et al.[2021]

A thorough assessment of nausea and vomiting in cancer patients is crucial, as it helps determine whether these symptoms are related to treatment or have other causes, which can lead to more effective interventions.

Recent clinical trials suggest that olanzapine is a promising option for preventing and treating chemotherapy-induced nausea and vomiting, complementing existing antiemetic guidelines that primarily reduce vomiting but not nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing Nausea and Vomiting in Patients With Cancer: What Works. Navari, RM.[2018]

In a phase II trial involving 51 patients with thoracic malignancies, a low dose of 5 mg olanzapine combined with granisetron and dexamethasone achieved a high complete response rate of 94% in preventing nausea and vomiting after carboplatin chemotherapy.

The treatment was well-tolerated, with no severe adverse effects (grade 3 or higher) reported, indicating that this combination therapy is both effective and safe for patients undergoing high-dose carboplatin regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial. Sakai, C., Shimokawa, M., Iihara, H., et al.[2021]

A high-dose dexamethasone regimen effectively reduced cis-platinum-induced nausea and vomiting in 50% of patients who had previously failed antiemetic treatments and in 71% of those who had not received prior antiemetics, indicating its efficacy as a treatment option.

The treatment was safe, with no significant side effects reported from the steroids, and its effectiveness remained consistent through multiple chemotherapy cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose dexamethasone for prevention of cis-platin-induced vomiting. Aapro, MS., Alberts, DS.[2019]

In a study of 81 gynecologic cancer patients receiving chemotherapy, the addition of olanzapine, with or without dexamethasone, did not significantly improve the prevention of delayed nausea and vomiting compared to standard dexamethasone treatment.

The overall control of delayed emesis was similar across all treatment groups, indicating that the olanzapine regimens did not provide additional benefits in managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course olanzapine to prevent delayed emesis following carboplatin/paclitaxel for gynecologic cancer: a randomised study. Celio, L., Saibene, G., Lepori, S., et al.[2022]

This study aims to confirm that sparing dexamethasone (DEX) after the first day of chemotherapy is non-inferior when combined with neurokinin-1 receptor antagonist (NK1-RA), palonosetron (Palo), and olanzapine (OLZ) for patients receiving cisplatin-based highly emetogenic chemotherapy (HEC).

The trial will involve 280 patients and assess the complete response rate (no vomiting and no need for rescue medications) during the delayed phase after chemotherapy, with a non-inferiority margin set at -15.0%, indicating a focus on maintaining efficacy while potentially reducing DEX-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1-4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy. Minatogawa, H., Izawa, N., Kawaguchi, T., et al.[2021]

In a phase II study involving 51 chemotherapy-naïve patients receiving cisplatin, the combination of olanzapine, palonosetron, and dexamethasone resulted in a complete response rate of only 43%, which did not meet the expected efficacy threshold for preventing nausea and vomiting.

While the treatment was not effective in preventing chemotherapy-induced nausea and vomiting, it was generally safe, with somnolence reported in 73% of patients, though most tolerated it well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of prophylactic olanzapine combined with palonosetron and dexamethasone for preventing nausea and vomiting induced by cisplatin. Maeda, A., Ura, T., Asano, C., et al.[2022]

Olanzapine is effective in reducing nausea in cancer patients undergoing treatment, although it may cause sedation, which can be a drawback.

There are no significant differences in effectiveness or tolerability among various serotonin and neurokinin receptor antagonists, suggesting that drug selection should prioritize cost, potential interactions, and ease of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nausea and vomiting induced by antineoplastic therapy]. Petersen, PC., Ruhlmann, C., Herrstedt, J.[2020]

In a study of 40 colorectal cancer patients undergoing oxaliplatin-based chemotherapy, the combination of olanzapine with other antiemetics was found to be safe, with the most common side effect being mild somnolence in 17.5% of patients.

The antiemetic regimen resulted in a high efficacy rate, with 86.1% of patients achieving complete response and no vomiting reported in the first 120 hours after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of the safety of olanzapine for oxaliplatin based chemotherapy in coloraectal patients. Nishimura, J., Hasegawa, A., Kudo, T., et al.[2021]

In a study of 47 patients undergoing non-cisplatin-containing chemotherapy, ondansetron combined with dexamethasone achieved a 97% success rate in controlling acute vomiting, significantly outperforming the 82% success rate of tropisetron with dexamethasone (p = 0.026).

Both ondansetron and tropisetron, when used with dexamethasone, were effective in preventing vomiting, but further research with a double-blind design is needed to explore potential pharmacological differences between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron and tropisetron with dexamethasone in the prophylaxis of acute vomiting induced by non-cisplatin-containing chemotherapy. Jantunen, IT., Kataja, VV., Johansson, RT.[2019]

In a study of 40 pediatric patients receiving chemotherapy, adding olanzapine to the standard anti-nausea treatment of ondansetron and dexamethasone did not improve the prevention of chemotherapy-induced nausea and vomiting (CINV).

Patients receiving olanzapine experienced a higher rate of minor side effects, indicating that the addition of olanzapine may not only be ineffective but could also lead to increased adverse effects in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Adding Olanzapine to the Standard Preventive Regimen for Chemotherapy-induced Nausea and Vomiting in Children: A Randomized Double-blind Controlled Trial. Moshayedi, M., Salehifar, E., Karami, H., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Neutropenic sepsis rates in patients receiving bleomycin, etoposide and cisplatin chemotherapy using olanzapine and reduced doses of dexamethasone compared to a standard antiemetic regimen. [2021]

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

Managing Nausea and Vomiting in Patients With Cancer: What Works. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

High-dose dexamethasone for prevention of cis-platin-induced vomiting. [2019]

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

Short-course olanzapine to prevent delayed emesis following carboplatin/paclitaxel for gynecologic cancer: a randomised study. [2022]

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

Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1-4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy. [2021]

7. Australia pubmed.ncbi.nlm.nih.gov

A phase II trial of prophylactic olanzapine combined with palonosetron and dexamethasone for preventing nausea and vomiting induced by cisplatin. [2022]

8. Denmark pubmed.ncbi.nlm.nih.gov

[Nausea and vomiting induced by antineoplastic therapy]. [2020]

9. England pubmed.ncbi.nlm.nih.gov

A phase II study of the safety of olanzapine for oxaliplatin based chemotherapy in coloraectal patients. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Ondansetron and tropisetron with dexamethasone in the prophylaxis of acute vomiting induced by non-cisplatin-containing chemotherapy. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Adding Olanzapine to the Standard Preventive Regimen for Chemotherapy-induced Nausea and Vomiting in Children: A Randomized Double-blind Controlled Trial. [2021]