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

Sponsor

Blokhin's Russian Cancer Research Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03478605

Collaborator

RUSSCO/RakFond (Other)

130

Enrollment

Location

Arms

12.2

Anticipated Duration (Months)

10.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Emesis Vomiting Nausea Post Chemotherapy Nausea Chemotherapy-induced Nausea and Vomiting	Drug: Olanzapine Drug: Aprepitant Pill Drug: Ondansetron Drug: Dexamethasone	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase II randomized trialPhase II randomized trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 25, 2018

Anticipated Primary Completion Date :

May 25, 2019

Anticipated Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Olanzapine 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;	Drug: Olanzapine Olanzapine 5 mg/day will be administered orally on days 0-4 of chemotherapy cycle (before bedtime) Other Names: Zyprexa Drug: Ondansetron Ondansetron 16 mg IV on day 1 of chemotherapy cycle (as standard component of antiemetic therapy) Drug: Dexamethasone Dexamethasone 8 mg IV on day 1 of chemotherapy cycle; 8 mg IV or orally on days 2-3 (as standard component of antiemetic therapy)
Active Comparator: Aprepitant 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;	Drug: Aprepitant Pill Aprepitant 125 mg orally will be administered on day 1 of chemotherapy cycle; 80 mg - on days 2 and 3. Other Names: Emend Drug: Ondansetron Ondansetron 16 mg IV on day 1 of chemotherapy cycle (as standard component of antiemetic therapy) Drug: Dexamethasone Dexamethasone 8 mg IV on day 1 of chemotherapy cycle; 8 mg IV or orally on days 2-3 (as standard component of antiemetic therapy)

Arm

Intervention/Treatment

Experimental: Olanzapine

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;

Drug: Olanzapine

Olanzapine 5 mg/day will be administered orally on days 0-4 of chemotherapy cycle (before bedtime)

Other Names:

Zyprexa

Drug: Ondansetron

Ondansetron 16 mg IV on day 1 of chemotherapy cycle (as standard component of antiemetic therapy)

Drug: Dexamethasone

Dexamethasone 8 mg IV on day 1 of chemotherapy cycle; 8 mg IV or orally on days 2-3 (as standard component of antiemetic therapy)

Active Comparator: Aprepitant

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;

Drug: Aprepitant Pill

Aprepitant 125 mg orally will be administered on day 1 of chemotherapy cycle; 80 mg - on days 2 and 3.

Other Names:

Emend

Drug: Ondansetron

Ondansetron 16 mg IV on day 1 of chemotherapy cycle (as standard component of antiemetic therapy)

Drug: Dexamethasone

Dexamethasone 8 mg IV on day 1 of chemotherapy cycle; 8 mg IV or orally on days 2-3 (as standard component of antiemetic therapy)

Outcome Measures

Primary Outcome Measures

Nausea control [0-120 hours after chemotherapy]
Complete control of nausea (ie, no nausea) in overall treatment period (0-120 hours after chemotherapy).

Secondary Outcome Measures

Complete Response Rate in Overall Treatment Period [0-120 hours after chemotherapy]
Complete response rate (ie, no vomiting, no use of rescue medication) in 0-120 hours after chemotherapy
Rate of undesired sedation [0-120 hours after chemotherapy]
Rate of undesired sedation 0-120 hours after chemotherapy
Complete Response Rate in Acute Treatment Period [0-24 hours after chemotherapy]
Complete response rate (ie, no vomiting, no use of rescue medication) in 0-24 hours after chemotherapy
Complete Response Rate in Delayed Treatment Period [24-120 hours after chemotherapy]
Complete response rate (ie, no vomiting, no use of rescue medication) in 24-120 hours after chemotherapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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);
Administration of HEC component only in first day of the cycle;
No previous chemotherapy or radiotherapy;
No concomitant quinolone antibiotics administration;
ECOG PS ≤2;
No nausea and vomiting 24 hours before enrollment;
Adequate hepatic and renal function (eg, ALaT, ASaT ≤3 ULN, creatinine clearance ≥50 ml/minute).
No brain metastases, leptomeningeal carcinomatosis, and chronic diseases such as uncontrolled diabetes mellitus and chronic alcohol consumption.
Subject willing to participate in the trial and provided informed consent form.

Exclusion Criteria:

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