Clinical trial NCT03478605: Trial to Evaluate Efficacy of Olanzapine With Short-acting 5HT3 Inhibitors in Chemotherapy-induced Nausea & Vomiting (CINV) Prophylaxis
Official title: Phase II Randomized Trial to Evaluate Efficacy of Olanzapine With Short-acting 5HT3 Inhibitors in Chemotherapy-induced Nausea & Vomiting (CINV) Prophylaxis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Emesis
Vomiting
Nausea Post Chemotherapy
Nausea
Chemotherapy-induced Nausea and Vomiting
Keywords: olanzapine
aprepitant
CINV
nausea
vomiting
nausea and vomiting
antiemetics
Lead sponsor: Blokhin's Russian Cancer Research Center
Sponsor class: OTHER
Collaborators: name: RUSSCO/RakFond
First posted: 2018-03-27
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase II randomized trial
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Nausea control
timeFrame: 0-120 hours after chemotherapy
Secondary outcomes:
measure: Complete Response Rate in Overall Treatment Period
timeFrame: 0-120 hours after chemotherapy
measure: Rate of undesired sedation
timeFrame: 0-120 hours after chemotherapy
measure: Complete Response Rate in Acute Treatment Period
timeFrame: 0-24 hours after chemotherapy
measure: Complete Response Rate in Delayed Treatment Period
timeFrame: 24-120 hours after chemotherapy
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: N.N. Blokhin Cancer Research Center
Study officials:
References: