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Low Dose Olanzapine to the Prophylaxis of Nausea and Vomiting Induced by Chemotherapy in Children and Adolescents (OZONE-V)

Primary Purpose

Chemotherapy-induced Nausea and Vomiting

Status

Recruiting

Phase

Phase 3

Locations

Russian Federation

Study Type

Interventional

Intervention

Ondansetron

Dexamethasone

Aprepitant

Olanzapine

About this trial

This is an interventional treatment trial for Chemotherapy-induced Nausea and Vomiting

Eligibility Criteria

5 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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.

Sites / Locations

Zhukov NikolayRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control group

Olanzapine

Arm Description

Weight category 30-40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg) 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.

Weight category 30-40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg), olanzapine (2.5 mg) 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.

Outcomes

Primary Outcome Measures

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

Patient preference

Proportion of patients who, after crossover, chose to continue treatment with an experimental regimen including olanzapine

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]

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT05346731

First Posted

April 14, 2022

Last Updated

July 27, 2022

Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

1. Study Identification

Unique Protocol Identification Number

NCT05346731

Brief Title

Low Dose Olanzapine to the Prophylaxis of Nausea and Vomiting Induced by Chemotherapy in Children and Adolescents

Acronym

OZONE-V

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 1, 2022 (Actual)

Primary Completion Date

March 2024 (Anticipated)

Study Completion Date

August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chemotherapy-induced Nausea and Vomiting

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

210 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Control group

Arm Type

Active Comparator

Arm Description

Arm Title

Olanzapine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ondansetron

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

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;

Intervention Type

Drug

Intervention Name(s)

Aprepitant

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Olanzapine

Intervention Description

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).

Primary Outcome Measure Information:

Title

Complete control of vomiting

Description

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

Time Frame

up to 21 days

Title

Patient preference

Description

Proportion of patients who, after crossover, chose to continue treatment with an experimental regimen including olanzapine

Time Frame

up to 42 days

Title

Adverce events

Description

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]

Time Frame

up to 42 days

Secondary Outcome Measure Information:

Title

Complete control of acute vomiting

Description

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

Time Frame

up to 21 days

Title

Complete control of chemotherapy-induced nausea and vomiting (CINV)

Description

Time Frame

up to 21 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nikolay Zhukov, MD,PhD

Phone

+79264177766

1cancerdoctor1@gmail.com

Facility Information:

Facility Name

Zhukov Nikolay

City

Moscow

ZIP/Postal Code

117997

Country

Russian Federation

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nikolay Zhukov, MD, PhD

Phone

+79264177766

1cancerdoctor1@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Low Dose Olanzapine to the Prophylaxis of Nausea and Vomiting Induced by Chemotherapy in Children and Adolescents

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