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

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

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

Study Overview

• Status: Unknown
• Conditions: Chemotherapy-induced Nausea and Vomiting; Nausea; Vomiting; Emesis; Nausea Post Chemotherapy
• Intervention / Treatment: Drug: Olanzapine; Drug: Ondansetron; Drug: Dexamethasone; Drug: Aprepitant Pill

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 Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Recruiting
    • N.N. Blokhin Cancer Research Center
    • Contact: Alexey A Rumyantsev, MD; Phone Number: +79100022255; Email: alexeymma@gmail.com
    • Principal Investigator: Alexey A Rumyantsev, MD
    • Principal Investigator: Ilya A Pokataev, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: 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); 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nausea control	Complete control of nausea (ie, no nausea) in overall treatment period (0-120 hours after chemotherapy).	0-120 hours after chemotherapy

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center
• Collaborators: RUSSCO/RakFond

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Anticipated): May 25, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 5, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: nausea; olanzapine; vomiting; aprepitant; nausea and vomiting; CINV; antiemetics
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Olanzapine; Ondansetron; Aprepitant
• Other Study ID Numbers: OlaCINV; 2018-01-YS-ECI (Other Grant/Funding Number: RUSSCO/RakFond)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No