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

Trial Summary

What is the purpose of this trial?

Chemotherapy-induced nausea and vomiting (CINV) are among the most bothersome symptoms during cancer treatment according to children and their parents. Most children receiving highly emetogenic chemotherapy (HEC), including those receiving hematopoietic stem cell transplant (HSCT) conditioning, experience CIV despite receiving antiemetic prophylaxis. Olanzapine improves CINV control in adult cancer patients, has a track record of safe use in children with psychiatric illness, does not interact with chemotherapy and is inexpensive. We hypothesize that the addition of olanzapine to standard antiemetics will improve chemotherapy-induced vomiting (CIV) control in children receiving highly emetogenic chemotherapy

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.

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

Research shows that Olanzapine can help manage nausea and vomiting in cancer patients, especially when other medications don't work. In studies, it completely resolved vomiting in some patients and improved appetite, with no reported side effects. ^{1 2 3 4 5}

Is olanzapine safe for humans?

Olanzapine has been used in cancer patients to manage nausea and vomiting, and studies have reported no adverse effects related to its use in these cases. ^{1 2 3 4 5}

How does the drug olanzapine differ from other treatments for cancer-related nausea and vomiting?

Olanzapine is unique because it is originally an antipsychotic drug used for conditions like schizophrenia, but it has been found effective for treating nausea and vomiting in cancer patients, especially when other standard treatments fail. It works by affecting multiple neurotransmitter receptors, which helps control these symptoms. ^{1 3 4 5 6}

Research Team

Lee Dupuis, RPh, PhD

Principal Investigator

The Hospital for Sick Children

Muhammad Ali

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

References

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

Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. [2022]

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

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

3. Thailand pubmed.ncbi.nlm.nih.gov

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

4. Japan pubmed.ncbi.nlm.nih.gov

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

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

Efficacy of Olanzapine for Symptom Relief in Cancer Patients. [2023]

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

A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients. [2019]