Olanzapine for Cancer-Related Nausea and Vomiting

Recruiting at 8 trial locations

Overseen By Muhammad Ali, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: The Hospital for Sick Children

Must be taking: Antiemetics

Disqualifiers: Pregnancy, ECG abnormalities, others

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: Unknown

Duration: 8 days

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding olanzapine, a medication, to standard treatments can better control nausea and vomiting in children undergoing strong chemotherapy. Chemotherapy often causes these uncomfortable symptoms, even with preventive medicines. Participants will receive either olanzapine or a placebo alongside their usual anti-nausea medication. Children who are set to receive strong chemotherapy and weigh at least 12.5 kg might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that olanzapine will be added to standard antiemetics (medications that prevent nausea and vomiting), so you may continue those.

Is there any evidence suggesting that olanzapine is likely to be safe for children in this trial?

Research has shown that olanzapine is safe for use. Studies have found that olanzapine can significantly reduce nausea and vomiting during chemotherapy. In one study, 70% of patients who took olanzapine did not experience vomiting, and 68% did not feel nauseous, marking a significant improvement compared to those who did not take olanzapine.

Olanzapine has been safely used in children with mental health conditions, indicating it is generally well-tolerated. It does not interfere with chemotherapy, which is beneficial. While any medication can have side effects, evidence suggests that olanzapine is a safe choice for managing nausea and vomiting caused by chemotherapy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer-related nausea and vomiting?

Olanzapine is unique because it targets cancer-related nausea and vomiting by acting on multiple neurotransmitter pathways, which is different from most standard treatments like serotonin or dopamine antagonists. This broad mechanism of action allows olanzapine to potentially address a wider range of nausea symptoms. Researchers are excited about olanzapine because it may offer more comprehensive relief for patients who don't respond well to existing antiemetics, providing a new option with potentially enhanced effectiveness.

What evidence suggests that olanzapine might be an effective treatment for chemotherapy-induced nausea and vomiting?

Research has shown that olanzapine helps reduce nausea and vomiting in cancer patients. In this trial, participants will receive either standard antiemetics plus olanzapine or standard antiemetics plus a placebo. One study found that 70% of patients who took olanzapine did not experience vomiting, and 68% did not feel nauseous. Another study showed that olanzapine was more effective than a placebo in preventing nausea. Additionally, various studies have demonstrated that small doses of olanzapine effectively reduce nausea. Overall, olanzapine has a strong record of controlling nausea and vomiting in adults receiving cancer treatment. ^{2 3 4 6 7}

Who Is on the Research Team?

Lee Dupuis, RPh, PhD

Principal Investigator

The Hospital for Sick Children

Muhammad Ali

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for children aged 2.5 to <18 who are about to receive high-dose chemotherapy or stem cell transplant conditioning and weigh at least 12.5 kg. They must have normal kidney function, liver enzymes, and ECG results, with no severe heart issues. Girls of childbearing age need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

I am not pregnant.

My liver enzyme ALT levels are within 5 times the normal range.

Patients of childbearing potential must consent to use adequate contraception (males and females) or agree to practice abstinence

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard antiemetics plus olanzapine or placebo during chemotherapy

8 days

Daily visits during chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and impact on HSCT outcomes

up to 1 month

Extended Follow-up

Monitoring of HSCT outcomes, including incidence of GVHD and veno-occlusive disease

100 days post-HSCT

What Are the Treatments Tested in This Trial?

Interventions

• Olanzapine

Trial Overview The study tests if Olanzapine added to standard anti-nausea drugs can better prevent vomiting caused by strong chemotherapy in kids compared to a placebo (fake pill). Participants will be randomly assigned either the medication or placebo during their hospital stay.

How Is the Trial Designed?

Group I: Olanzapine Active Control 1 Intervention

Standard antiemetics plus olanzapine

Group II: Placebo Oral Tablet Placebo Group 1 Intervention

Standard antiemetics plus placebo

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Children's Mercy Hospital Kansas City

Collaborator

Trials

261

Recruited

941,000+

St. Justine's Hospital

Collaborator

Trials

205

Recruited

87,300+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

CancerCare Manitoba

Collaborator

Trials

29

Recruited

5,600+

Published Research Related to This Trial

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]

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 review of 28 patients receiving olanzapine for delayed emesis prevention during chemotherapy, the drug was well tolerated with few side effects, indicating its safety for this use.

Olanzapine may effectively reduce the incidence of delayed emesis, with only 22.1% of patients experiencing nausea and 10.5% experiencing vomiting during 95 chemotherapy cycles, suggesting it could be a beneficial treatment option for patients undergoing moderately to highly emetogenic chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. Passik, SD., Kirsh, KL., Theobald, DE., 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]

Citations

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

Olanzapine for the Prevention and Treatment of ... The results showed that 39 of 56 (70%) patients treated with olanzapine had no vomiting and 38 (68%) had no nausea, compared with 16 of 52 (31%) ...

2. 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.

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

Dose-dependent Efficacy of Olanzapine for Chemotherapy ... Sato et al. (7) reported that concurrent administration of olanzapine at 2.5 mg/day improved nausea, whereas Uchiike et al. (8) reported that improvement in ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2765323

Olanzapine for the Treatment of Advanced Cancer ... The data from this trial support that olanzapine substantially decreases nausea/vomiting associated with advanced cancer and is relatively well ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2020/olanzapine-reduces-nausea-advanced-cancer

Olanzapine Reduces Nausea Caused by Advanced Cancer In a small NCI-funded study, treatment with olanzapine (Zyprexa) greatly reduced cancer patients' nausea and vomiting compared with a placebo.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6513437/

Olanzapine for the prevention and treatment of cancer‐related ... Olanzapine probably doubles the likelihood of no nausea or vomiting during chemotherapy from 25% to 50% (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.59 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925002187?dgcid=rss_sd_all

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