Olanzapine vs Dexamethasone for Chemo-Related Nausea and Vomiting

Recruiting in Sayre (>99 mi)

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

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two drugs, olanzapine and dexamethasone, to determine which better prevents nausea and vomiting caused by chemotherapy. Both drugs currently address this issue, but researchers aim to assess if olanzapine is as effective as dexamethasone. Individuals diagnosed with cancer and about to begin chemotherapy known to cause nausea might be suitable for this trial. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments benefit a broader range of patients.

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 is the safety track record for these treatments?

Research has shown that both olanzapine and dexamethasone are generally safe for treating nausea and vomiting caused by chemotherapy.

Olanzapine effectively reduces these symptoms, though some patients report feeling sleepy or dizzy. These side effects are the most common but are usually mild.

Dexamethasone, a type of steroid, is also commonly used for the same purpose and is considered safe. Studies indicate that different dosing schedules of dexamethasone do not affect its safety. Both drugs are part of standard care and are recommended in guidelines for managing chemotherapy-related nausea and vomiting. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they offer new approaches to managing chemotherapy-related nausea and vomiting, a condition typically treated with drugs like ondansetron or aprepitant. Olanzapine, commonly used as an antipsychotic, is being explored for its ability to block multiple neurotransmitters involved in nausea, which could offer broader relief than traditional options. Dexamethasone, a corticosteroid, is already used for its anti-inflammatory properties, but this trial investigates its effectiveness in different dosing schedules. Combining these treatments may enhance their effectiveness and provide patients with faster and more comprehensive symptom control.

What is the effectiveness track record for olanzapine and dexamethasone in treating chemo-related nausea and vomiting?

This trial will compare the effectiveness of olanzapine and dexamethasone in preventing chemotherapy-related nausea and vomiting. Studies have shown that both drugs work well for this purpose. Participants in one arm of the trial will receive olanzapine, which has been proven to greatly reduce nausea and increase the number of patients who do not experience nausea and vomiting compared to those taking a placebo. Research shows that olanzapine is especially effective when added to standard treatments. Participants in the other arm will receive dexamethasone, which also yields strong results, with many patients finding relief from nausea and vomiting after chemotherapy, particularly in the first few days. Medical guidelines recommend both drugs for treating chemotherapy-related nausea and vomiting. ^{6 7 8 9 10}

Who Is on the Research Team?

Zane Waite, PharmD, BCOP

Principal Investigator

The Guthrie Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39463560/

Dexamethasone-Sparing Antiemetic Prophylaxis for ... The regimen demonstrated exceptional efficacy with a 96.9% overall response rate across all cycles. Complete control rates for acute CINV were ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225000747

A systemic review on chemotherapy induced nausea and ... Up to 60 % of patients still experience delayed nausea, and anticipatory nausea and vomiting affect up to 30 % and 20 % of patients, respectively, by the fourth ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6975929/

A Systematic Review and Individual Patient Data‐Based ... This IPD meta‐analysis indicates that the dexamethasone‐sparing regimen is not associated with a significant loss in overall antiemetic control in patients ...

4. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.12072

Single low-dose 5-mg versus 8-mg dexamethasone with ... This study identify single low-dose 5mg DEX is equally effective as 8mg DEX with NEPA for the 168h Prevention of HEC or MEC (high-risk patients) CINV.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772906024003431

Advancements in managing chemotherapy-induced ... Per the guidelines, the pattern involves dexamethasone to last for the first 4 days, then 3 days during each subsequent cycle to prevent nausea and vomiting.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39340704/

Efficacy and safety of dexamethasone sparing for the ... Efficacy and safety of dexamethasone sparing for the prevention of nausea and vomiting associated with highly emetogenic risk antineoplastic ...

7. ascopubs.org ascopubs.org/doi/10.1200/GO.23.00301

Dexamethasone-Free Antiemetic Prophylaxis for Highly ... This study demonstrates the efficacy and safety of a DEX-free chemotherapy-induced nausea and vomiting prophylaxis regimen for patients ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0305737223000038

Efficacy and safety of antiemetic regimens for highly ... Chemotherapy-induced nausea and vomiting (CINV) are common and distressing side effects. 70 % to 80 % of cancer patients receiving chemotherapy develop CINV; ...

9. jhmhp.amegroups.org jhmhp.amegroups.org/article/view/4296/html

Efficacy and safety of 1-day versus 3-day dexamethasone for ... We find that the 1-day dexamethasone therapy provides a similar efficacy and safety profile as a treatment of 3-day dexamethasone in the prophylaxis of CINV.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT01012336

NCT01012336 | Safety and Efficacy of Aprepitant, ... Incidence of chemotherapy induced nausea and vomiting (CINV) is approximately 50% in patients receiving MEC. An incidence rate of 25-38% for delayed emesis and ...