"Olanzapine for Prevention of Chemotherapy Induced Nausea and Vomiting in Children and Adolescents Receiving Highly Emetogenic Chemotherapy (HEC)"

NCT03219710 | Completed Phase 3

• 1 other identifier: IECPG-151/26.04.2017
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Chemotherapy induced nausea and vomiting (CINV) is one of the most distressing toxicities of cancer treatment. It can occur up to 90% in case of highly emetogenic chemotherapy (HEC) use. It is important to effectively manage CINV for a number of reasons. Acute phase vomiting can lead to vomiting in the delayed phase. It causes poor compliance with further therapy. Quality of life is compromised. It is easier to prevent nausea/vomiting than to treat it. Though strategies for prevention of CINV have been improved, it is still a significant problem. Newer drugs were explored and studied. The complete response rates were further increased with usage of olanzapine, an FDA approved antipsychotic, which blocks multiple neurotransmitters in the central nervous system. Olanzapine has been studied in multiple randomized trials in adults for its safety and efficacy in prevention of CINV. Various RCTs have demonstrated the superiority of olanzapine for prevention of CINV in patients receiving highly and moderately emetogenic chemotherapy. Olanzapine has been approved for prevention of CINV in adults. Unfortunately there are no large randomized trials demonstrating the efficacy of olanzapine for CINV prevention in children receiving HEC. The positive experience with olanzapine reported in adult oncology patients has prompted some pediatric clinicians to prescribe olanzapine for individual children receiving chemotherapy. Olanzapine is frequently used for the treatment of schizophrenia and bipolar disorder in children and adolescents. Though various studies have demonstrated safety of olanzapine in children, data regarding the efficacy of olanzapine in children and adolescents for prevention of CINV is limited. There are many small studies describing the safety and efficacy of olanzapine for prevention of CINV. However, there are no large randomized trials. Olanzapine is available in generic form and is not an expensive drug. Therefore we would like to conduct a randomized trial to look for the efficacy of olanzapine in pediatric population for prevention of CINV

Conditions

Chemotherapy-induced Nausea and Vomiting

Keywords

Chemotherapy induced nausea and vomiting; olanzapine

Outcome Measures

Primary Outcomes (3)

• The number of patients with no episodes of vomiting as assessed by CTCAE v4.03 till 120 hours after highly emetogenic chemotherapy.

  The number of patients achieving complete response as defined as, no episode of vomiting , assessed by CTCAE v.4.03 will be compared between the groups.

  120 hours after administration of chemotherapy.

• The number of patients with no episodes of vomiting as assessed by CTCAE v.03 till 24 hours after highly emetogenic chemotherapy.

  The number of patients achieving complete response: defined as, no episode of vomiting , assessed by CTCAE v.4.03 will be compared between the groups.

  Till 24 hours after administration of chemotherapy.

• The number of patients with no episodes of vomiting as assessed by CTCAE v4.03after 24 hours till 120 hours post highly emetogenic chemotherapy.

  The number of patients achieving complete response as defined as, no episode of vomiting , assessed by CTCAE v.4.03 will be compared between the groups.

  From 24 hours till 120 hours post administration of chemotherapy.

Secondary Outcomes (3)

• The number of patients with no episodes of nausea as assessed by "Edmonton symptom assessment scale" till 24 hours after highly emetogenic chemotherapy.

  Till 24 hours after administration of chemotherapy.

• The number of patients with no episodes of nausea as assessed by "Edmonton symptom assessment scale" after 24 hours till 120 hours post highly emetogenic chemotherapy.

  After 24 hours till 120 hours post administration of chemotherapy.

• The number of patients with no episodes of nausea as assessed by "Edmonton symptom assessment scale" till 120 hours post highly emetogenic chemotherapy.

  Till 120 hours after administration of chemotherapy.

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Patient on control group (ODA) with weight category of 15-40 kg will receive: D1-D3 Dexamethasone 3 mg/m2, ondansetron (0.15 mg/kg,), Aprepitant 80 mg; The patient on control group with weight category of \> 40 kg will receive: D1- Dexamethasone 3 mg/m2 , ondansetron(0.15 mg/kg ), Aprepitant 125 mg; D2-D3 Dexamethasone 3mg/m2, ondansetron (0.15 mg/kg,), Aprepitant 80 mg Note: Aprepitant will be administered as single oral dose, dexamethasone and ondansetron will be administered q 8h (PO/IV)

Drug: Ondansetron; Drug: Dexamethasone; Drug: Aprepitant

Arm B

EXPERIMENTAL

weight category of 15-40 kg will receive: D1-D3 Dexamethasone 3mg/m2, ondansetron (0.15 mg/kg,), Aprepitant 80 mg and olanzapine 0.14mg/kg (rounded off to nearest 2.5 mg) D4-olanzapine 0.14mg/kg (rounded off to nearest 2.5 mg) Weight category of \> 40 kg in study group will receive: D1- Dexamethasone 3mg/m2, ondansetron (0.15 mg/kg, ), Aprepitant 125 mg; olanzapine 0.14mg/kg (rounded off to nearest 2.5 mg) D2-D3 Dexamethasone 3mg/m2, ondansetron (0.15 mg/kg,), Aprepitant 80 mg; olanzapine 0.14mg/kg (rounded off to nearest 2.5 mg) D4-olanzapine 0.14mg/kg (rounded off to nearest 2.5 mg) Note: Aprepitant \& Olanzapine will be administered as single oral dose, dexamethasone and ondansetron will be administered q 8h (PO/IV)

Drug: Ondansetron; Drug: Dexamethasone; Drug: Aprepitant; Drug: Olanzapine

Interventions

Ondansetron DRUG

Ondansetron will be given at a dosage of 0.15mg/kg IV/PO q8h.

Arm A; Arm B

Dexamethasone DRUG

Dexamethasone will be given as 3mg/m2 IV/PO q8h.

Arm A; Arm B

Aprepitant DRUG

Aprepitant will be given as per the weight. weight (15-40kg) - Day1 to Day 3 - 80 mg PO weight (\>40 kg) - Day 1 -125mg , Day 2 \& Day 3 - 80 mg PO

Arm A; Arm B

Olanzapine DRUG

olanzapine will be given as 0.14mg/kg PO (rounded off to nearest 2.5 mg )

Arm B

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age group 5-18 years with weight between ≥15 kg
• All subjects must have a confirmed diagnosis of malignancy
• European Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
• Scheduled to receive highly emetogenic chemotherapy as assessed using the Pediatric Oncology Group of Ontario Guideline for emetogenicity Classification
• Patients receiving first cycle of chemotherapy
• Children's caregiver who can understand Hindi or English and are willing to participate in the study (with written informed consent)

You may not qualify if:

• Have had treatment within 14 days prior to study enrollment with olanzapine or 30 days prior to study enrollment with another antipsychotic agent
• Planned to receive quinolone antibiotics while receiving olanzapine
• Have uncontrolled hypertension
• Receive other antipsychotic agents, amifostine, citalopram, CYP1A2 inducers or inhibitors
• Have a history of neuroleptic malignant syndrome, a seizure disorder, hypersensitivity to olanzapine.
• Children with known cardiac disease
• Are pregnant or breast-feeding
• Had received or will receive RT to abdomen or pelvis in the week prior to treatment
• Vomited in the 24 hours prior to study
• Previous exposure to HEC
• Abnormal lab values (ANC\<1500/mm3, TLC\<3000/mm3, Plt\<100,000/mm3, AST/ALT\> 2.5 times of ULN, bill\>1.5 times of ULN, S.cr\>1.5 times of ULN, patient on systemic steroids

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (1)

Dr Bra Irch, Aiims, New Delhi

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Related Publications (1)

• Naik RD, V S, Singh V, Pillai AS, Dhawan D, Bakhshi S. Olanzapine for Prevention of Vomiting in Children and Adolescents Receiving Highly Emetogenic Chemotherapy: Investigator-Initiated, Randomized, Open-Label Trial. J Clin Oncol. 2020 Nov 10;38(32):3785-3793. doi: 10.1200/JCO.20.00871. Epub 2020 Sep 15.

  PMID: 32931400 DERIVED

MeSH Terms

Conditions

Vomiting

Interventions

Ondansetron; Dexamethasone; Aprepitant; Olanzapine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Morpholines; Oxazines; Benzodiazepines; Benzazepines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: SENIOR RESIDENT

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: July 17, 2017
• Study Start: July 1, 2017
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: August 20, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)