Trial to Evaluate Efficacy of Olanzapine With Short-acting 5HT3 Inhibitors in Chemotherapy-induced Nausea & Vomiting (CINV) Prophylaxis (OlaCINV)

Blokhin's Russian Cancer Research Center

Status and phase: Unknown; Phase 2

Conditions: Vomiting; Nausea; Nausea Post Chemotherapy; Chemotherapy-induced Nausea and Vomiting; Emesis

Treatments: Drug: Dexamethasone; Drug: Ondansetron; Drug: Aprepitant Pill; Drug: Olanzapine

Study type: Interventional

Funder types: Other

Identifiers

NCT03478605

2018-01-YS-ECI (Other Grant/Funding Number)

OlaCINV

Details and patient eligibility

About

Olanzapine-containing regimens for CINV prophylaxis may provide even better protection than aprepitant-containing regimens.

Full description

Olanzapine-containing regimens for CINV provide high complete response (CR) rate in patients receiving high emetogenic chemotherapy. Olanzapine may be more effective than aprepitant in this setting but cheaper. However, there is no strong evidence supporting the advantages of olanzapine over aprepitant - and this is the reason why aprepitant is still the standard of care. Due to high cost aprepitant can be not affordable in low- and middle income countries; this compromises quality of life of cancer patients. On the other hand, recommended olanzapine-based regimen includes palonosetron, whose price is quite high as well and undesired sedation is a common side effect for olanzapine doses that currently recommended, these adverse events precludes wide use of olanzapine in oncology. Development of effective, tolerable and affordable regimen for CINV prophylaxis based on low-dose olanzapine and short-acting 5-HT3 inhibitors can improve quality of care for many cancer patients.

Enrollment: 130 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. High-emetogenic chemotherapy (HEC) regimen (e.g., cisplatin ≥70 mg/m2 or doxorubicin ≥60 mg/m2 or carboplatin AUC≥4). Patients that are prescribed less doses of mentioned agents are still allowed if another high-emetogenic drug will be administered (eg, doxorubicin plus cisplatin);
2. Administration of HEC component only in first day of the cycle;
3. No previous chemotherapy or radiotherapy;
4. No concomitant quinolone antibiotics administration;
5. ECOG PS ≤2;
6. No nausea and vomiting 24 hours before enrollment;
7. Adequate hepatic and renal function (eg, ALaT, ASaT ≤3 ULN, creatinine clearance ≥50 ml/minute).
8. No brain metastases, leptomeningeal carcinomatosis, and chronic diseases such as uncontrolled diabetes mellitus and chronic alcohol consumption.
9. Subject willing to participate in the trial and provided informed consent form.

Exclusion criteria

1. Previous chemotherapy or radiotherapy;
2. Moderate- or low- emetogenic chemotherapy;
3. Multiday administration of HEC agents;
4. ECOG PS >2;
5. History of brain metastases, signs of symptoms of bowel obstruction;
6. Nausea and/or vomiting of any genesis 24 hours before enrollment;
7. Uncontrolled diabetes mellitus or other metabolic diseases; chronic alcohol consumption.
8. Diseases and conditions interfere with subject ability to swallow the drug and to take oral medication;
9. Concomitant therapy with olanzapine or other antipsychotic drugs; history of mental illness;
10. Concomitant therapy with quinolone antibiotics;
11. Contraindications for olanzapine or aprepitant administration;
12. Intraperitoneal or intrapleural administration of HEC drugs;
13. Inadequate hepatic and/or renal function.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

Olanzapine

Experimental group

Description:

Olanzapine 5 mg/day p.o. d 0-4 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d.; IM or P.O. d 2-4;

Treatment:

Drug: Olanzapine

Drug: Ondansetron

Drug: Dexamethasone

Aprepitant

Active Comparator group

Description:

Aprepitant 125 mg p.o d 1 + 80 mg p.o d 2,3 + ondansetron 16 mg IV d 1 + dexamethasone 12 mg IV d 1, 8 mg b.i.d. IM or P.O. d 2-4;

Treatment:

Drug: Ondansetron

Drug: Aprepitant Pill

Drug: Dexamethasone