Chemotherapy-induced Nausea and VomitingPhase 3OZONE-VNCT05346731
Low Dose Olanzapine to the Prophylaxis of Nausea and Vomiting Induced by Chemotherapy in Children and Adolescents
A Phase 3 study testing Ondansetron, Dexamethasone and Aprepitant in people with Chemotherapy-induced Nausea and Vomiting, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial summary
Chemotherapy-induced nausea and vomiting continues to be a significant problem in children and adolescents. Standard antiemetic therapy, including a 5-HT3 antagonist, aprepitant, and a corticosteroid, achieves complete control in less than 50% of patients. Read more about this study
- Who is it for?
- Ages 5 to 18 years
- Conditions the study is for
- Chemotherapy-induced Nausea and Vomiting
- What is being tested?
- Ondansetron, Dexamethasone and Aprepitant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 1 siteRussia
- Study dates
- 1 Apr 2022to Aug 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age from 5 to 18 years.
- Body weight ≥ 30 kg.
- Confirmed diagnosis of malignancy.
- Planned at least 2 cycles of highly emetogenic chemotherapy according to the Pediatric Ontario Cancer Group (POGO) emetogenicity classification.
- ECOG status < 3.
- Adequate function of internal organs (bilirubin < 1.5 upper limit of normal (ULN), ALT and AST <2.5 ULN, creatinine < 1.5 ULN).
- Ability to swallow study drug.
- The presence of a written voluntary informed consent of the patient and / or his legal representative.
Who cannot join
- Treatment with olanzapine or another antipsychotic drug within the last 30 days.
- Planned use of antibiotics from the group of fluoroquinolones or other drugs that have drug interactions with olanzapine and other drugs used in the study (amifostin, citalopram, CYP1A2 inducers or inhibitors).
- The presence of intensive CINV against the background of a previous similar cycle of chemotherapy, which does not allow prescribing standard antiemetic prophylaxis upon inclusion in the study.
- The presence of a convulsive syndrome.
- Hypersensitivity to olanzapine or other drugs used in the study.
- Uncontrolled arterial hypertension or cardiovascular disorders, uncontrolled diabetes mellitus, or other diseases and conditions that, in the opinion of the physician, preclude study therapy.
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- The presence of other factors (other than ongoing highly emetogenic therapy) that can cause the development of CINV (radiotherapy to the abdominal cavity or pelvis 1 week or less before inclusion in the study, obstruction of the gastrointestinal tract, uncontrolled intracranial hypertension, etc.).
- Severe CINV of any intensity 24 hours or less before the first dose of chemotherapy.
- Pregnancy or breastfeeding.
- Planned use of systemic glucocorticosteroids at the time of inclusion in the study.
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Zhukov Nikolay
Moscow, 117997
Nikolay Zhukov, MD, PhD, +79264177766, 1cancerdoctor1@gmail.com
About this study
Official title: Efficacy and Safety Addition of Low Dose Olanzapine to the Standard Prophylaxis of Nausea and Vomiting Induced by Highly-emetogenic Chemotherapy in Children and Adolescents (OZONE-V)
Chemotherapy-induced nausea and vomiting continues to be a significant problem in children and adolescents. Standard antiemetic therapy, including a 5-HT3 antagonist, aprepitant, and a corticosteroid, achieves complete control in less than 50% of patients. Studies have shown that the addition of large doses of olanzapine improves control, including in children and adolescents. However, olanzapine has not yet been included in standard recommendations in the pediatric population. Studies in adults indicate that the dose of the drug can be halved without loss of effectiveness and with a decrease in toxicity. This open-label, randomized, phase III trial evaluates the efficacy and safety of adding low-dose olanzapine to standard prevention of nausea and vomiting induced by highly emetogenic chemotherapy in children and adolescents.
Read the detailed description
After signing informed consent, eligible patients are randomized with stratification (previously received or not received high emetogenic therapy; regimens with and without cisplatin) to receive the first cycle of highly emetogenic chemotherapy with standard prophylaxis (5-HT3 receptor antagonist, dexamethasone, aprepitant) with or without addition of 0.07 mg/kg olanzapine (rounded to multiples of 2.5 mg, maximum 5 mg). During chemotherapy and 120 hours after its completion, patients are assessed for the presence and absence, as well as the severity of CINV, the need for "rescue" therapy, and the development of adverse events. In the future, patients undergo a similar course of highly emetogenic chemotherapy with a change in the antiemetic prophylaxis option - crossover (patients who received an olanzapine regimen as antiemetic prophylaxis after the first cycle of chemotherapy receive treatment without it, patients who received prophylaxis without olanzapine receive a second cycle of therapy with olanzapine). After this cycle, the presence and absence, as well as the severity of CINV, the need for salvage therapy, the development of adverse events are assessed and, additionally, at the end of the cycle, patients are asked about the preferred option for further antiemetic prophylaxis (the regimen with olanzapine, no olanzapine, or no preferences).
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Being tested
- Ondansetron, Dexamethasone, Aprepitant, Olanzapine
- Medical subject headings
- Vomiting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OndansetronDrug
Ondnsetron will be administered at a dose of 0.15 mg/kg IV/PO every 8 hours on the day(s) of chemotherapy and 3 days after completion of chemotherapy
DexamethasoneDrug
Dexamethasone will be administered at a dose of 5 mg/m2 intravenously/orally once on the day(s) of chemotherapy and 3 days after completion of chemotherapy;
AprepitantDrug
Aprepitant will be administered based on body weight:
body weight 30-40 kg: days 1-3 - 80 mg orally; body weight > 40 kg: day 1 - 125 mg orally, days 2, 3 - 80 mg orally
OlanzapineDrug
Olanzapine will be administered at a dose of 0.07 mg/kg orally on the day(s) of chemotherapy and 3 days after completion of chemotherapy (rounded up to the maximum multiple of 2.5 mg, maximum daily dose of 5 mg).
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | 1. Weight category 30-40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg)
2. Weight category > 40 kg will receive:
dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (125 mg) Note: aprepitant at a dose of 80 mg/day. applied for another 2 days, regardless of the number of days of chemotherapy. Receives: Drug: Ondansetron; Drug: Dexamethasone; Drug: Aprepitant |
| Olanzapine | Experimental | 1. Weight category 30-40 kg will receive:
dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg), olanzapine (2.5 mg)
2. Weight category > 40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (125 mg), olanzapine (2.5 mg for <55 kg, 5 mg for >55 kg) Note: aprepitant at a dose of 80 mg/day. applied for another 2 days, regardless of the number of days of chemotherapy. Receives: Drug: Ondansetron; Drug: Dexamethasone; Drug: Aprepitant; Drug: Olanzapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete control of vomiting
proportion of patients who did not have episodes of vomiting and/or use of additional antiemetic drugs (rescue therapy) during the chemotherapy cycle and within 120 hours after its completion
Measured: up to 21 days
Patient preference
Proportion of patients who, after crossover, chose to continue treatment with an experimental regimen including olanzapine
Measured: up to 42 days
Adverce events
Percentage of patients with grade 3-4 adverse events according to CTCAE v. 5.0. [Time frame: day(s) of chemotherapy administration and 120 hours after chemotherapy administration]
Measured: up to 42 days
Secondary outcomes (2)
Complete control of acute vomiting
Proportion of patients who did not have episodes of vomiting and/or use of additional antiemetic drugs (rescue therapy) during the chemotherapy cycle and within 24 hours after its completion
Measured: up to 21 days
Complete control of chemotherapy-induced nausea and vomiting (CINV)
Proportion of patients who did not experience nausea (PeNAT score 1) and/or vomiting and/or use of additional antiemetics (rescue therapy) during the chemotherapy cycle and within 120 hours after its completion
Measured: up to 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2022
- Study start1 Apr 2022
- Primary completionMar 2024 (estimated)
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chemotherapy-induced Nausea and VomitingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05346731
- Sponsor's protocol ID
- OZONE-V
- Acronym
- OZONE-V
- Status last verified
- Jul 2022
- First submitted
- 14 Apr 2022
- Last updated
- 28 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety Addition of Low Dose Olanzapine to the Standard Prophylaxis of Nausea and Vomiting Induced by Highly-emetogenic Chemotherapy in Children and Adolescents (OZONE-V)
- ClinicalTrials.gov ID
- NCT05346731
- Acronym / sponsor ID
- OZONE-V / OZONE-V
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 26 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chemotherapy-induced nausea and vomiting continues to be a significant problem in children and adolescents. Standard antiemetic therapy, including a 5-HT3 antagonist, aprepitant, and a corticosteroid, achieves complete control in less than 50% of patients. Studies have shown that the addition of large doses of olanzapine improves control, including in children and adolescents. However, olanzapine has not yet been included in standard recommendations in the pediatric population. Studies in adults indicate that the dose of the drug can be halved without loss of effectiveness and with a decrease in toxicity. This open-label, randomized, phase III trial evaluates the efficacy and safety of adding low-dose olanzapine to standard prevention of nausea and vomiting induced by highly emetogenic chemotherapy in children and adolescents.
Detailed description
After signing informed consent, eligible patients are randomized with stratification (previously received or not received high emetogenic therapy; regimens with and without cisplatin) to receive the first cycle of highly emetogenic chemotherapy with standard prophylaxis (5-HT3 receptor antagonist, dexamethasone, aprepitant) with or without addition of 0.07 mg/kg olanzapine (rounded to multiples of 2.5 mg, maximum 5 mg). During chemotherapy and 120 hours after its completion, patients are assessed for the presence and absence, as well as the severity of CINV, the need for "rescue" therapy, and the development of adverse events. In the future, patients undergo a similar course of highly emetogenic chemotherapy with a change in the antiemetic prophylaxis option - crossover (patients who received an olanzapine regimen as antiemetic prophylaxis after the first cycle of chemotherapy receive treatment without it, patients who received prophylaxis without olanzapine receive a second cycle of therapy with olanzapine). After this cycle, the presence and absence, as well as the severity of CINV, the need for salvage therapy, the development of adverse events are assessed and, additionally, at the end of the cycle, patients are asked about the preferred option for further antiemetic prophylaxis (the regimen with olanzapine, no olanzapine, or no preferences).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Drug: Ondansetron, Drug: Dexamethasone, Drug: Aprepitant1. Weight category 30-40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg) 2. Weight category > 40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (125 mg) Note: aprepitant at a dose of 80 mg/day. applied for another 2 days, regardless of the number of days of chemotherapy. |
| Olanzapine | Experimental | Drug: Ondansetron, Drug: Dexamethasone, Drug: Aprepitant, Drug: Olanzapine1. Weight category 30-40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg), olanzapine (2.5 mg) 2. Weight category > 40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (125 mg), olanzapine (2.5 mg for <55 kg, 5 mg for >55 kg) Note: aprepitant at a dose of 80 mg/day. applied for another 2 days, regardless of the number of days of chemotherapy. |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Age from 5 to 18 years.
- Body weight ≥ 30 kg.
- Confirmed diagnosis of malignancy.
- Planned at least 2 cycles of highly emetogenic chemotherapy according to the Pediatric Ontario Cancer Group (POGO) emetogenicity classification.
- ECOG status < 3.
Key exclusion criteria (10 listed)
- Treatment with olanzapine or another antipsychotic drug within the last 30 days.
- Planned use of antibiotics from the group of fluoroquinolones or other drugs that have drug interactions with olanzapine and other drugs used in the study (amifostin, citalopram, CYP1A2 inducers or inhibitors).
- The presence of intensive CINV against the background of a previous similar cycle of chemotherapy, which does not allow prescribing standard antiemetic prophylaxis upon inclusion in the study.
- The presence of a convulsive syndrome.
- Hypersensitivity to olanzapine or other drugs used in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OndansetronOndnsetron will be administered at a dose of 0.15 mg/kg IV/PO every 8 hours on the day(s) of chemotherapy and 3 days after completion of chemotherapy | Drug | Control group, Olanzapine |
| DexamethasoneDexamethasone will be administered at a dose of 5 mg/m2 intravenously/orally once on the day(s) of chemotherapy and 3 days after completion of chemotherapy; | Drug | Control group, Olanzapine |
| AprepitantAprepitant will be administered based on body weight: body weight 30-40 kg: days 1-3 - 80 mg orally; body weight > 40 kg: day 1 - 125 mg orally, days 2, 3 - 80 mg orally | Drug | Control group, Olanzapine |
| OlanzapineOlanzapine will be administered at a dose of 0.07 mg/kg orally on the day(s) of chemotherapy and 3 days after completion of chemotherapy (rounded up to the maximum multiple of 2.5 mg, maximum daily dose of 5 mg). | Drug | Olanzapine |
Primary outcome
Complete control of vomiting
Time frame: up to 21 days
proportion of patients who did not have episodes of vomiting and/or use of additional antiemetic drugs (rescue therapy) during the chemotherapy cycle and within 120 hours after its completion
Patient preference
Time frame: up to 42 days
Proportion of patients who, after crossover, chose to continue treatment with an experimental regimen including olanzapine
Adverce events
Time frame: up to 42 days
Percentage of patients with grade 3-4 adverse events according to CTCAE v. 5.0. [Time frame: day(s) of chemotherapy administration and 120 hours after chemotherapy administration]
2 secondary outcomes
Complete control of acute vomiting
Time frame: up to 21 days
Complete control of chemotherapy-induced nausea and vomiting (CINV)
Time frame: up to 21 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ondansetron, Dexamethasone and Aprepitant in people with Chemotherapy-induced Nausea and Vomiting, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nikolay Zhukov, MD,PhD (+79264177766, 1cancerdoctor1@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete control of vomiting (time frame: up to 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2022.