Aprepitant Triple Therapy for the Prevention of CINV in Nondrinking and Young Women Who Received Moderately Emetogenic Chemotherapy (CINV)

Efficacy of Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Nondrinking Women Younger Than 50 Years Who Received Moderately Emetogenic Chemotherapy: A Randomized, Double-blind, Phase Ⅲ Trial

The purpose of this study is to study whether adding Aprepitant to Palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI or FOLFOX chemotherapy regimen among gastrointestinal malignancy patients with high risk factors of chemotherapy-associated adverse events.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Neoplasms; Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Aprepitant; Drug: Palonosetron; Drug: Dexamethasone; Drug: Placebo Oral Tablet

Detailed Description

The purpose of this study is to study whether adding Aprepitant to Palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI or FOLFOX chemotherapy regimen after curative effect among gastrointestinal malignancy patients with high risk factors of chemotherapy-associated adverse events.This study will observe and evaluate the incidence and severity of nausea and vomiting as well as the effectiveness of corresponding treatment(with or without Aprepitant) during Day 1 to Day 5 from the beginning of chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diagnosed by pathology as gastrointestinal carcinoma and no previous FOLFOX or FOLFIRI based regimen chemotherapy history.
• Female.
• Adult patients ( ≥ 18, ≤ 50 years of age)
• No long-term or excessive alcohol intake history:1.Alcohol intake less than 5 times per week; 2.Alcohol intake less than 100g per day.
• Performance status ECOG 0-1
• Adequate haematological, hepatic, renal and metabolic function parameters:

Leukocytes : 3,500-10,000/mm3, ANC ≥ 1,500/mm3, Platelets ≥ 90,000/mm3, Hb > 9g/dl (may be transfused or treated with erythropoietin to maintain or exceed this level), Serum creatinine ≤ 1 x upper limit of normal, Bilirubin ≤ 1.5 x upper limit of normal, Serum AST, ALT, ALP ≤ 2.5 x upper limit of normal in absence of liver metastases, or ≤ 5 x upper limit of normal in presence of liver metastases.

• Negative pregnancy test. If pregnancy test were positive, subject should be included in the trial only when the subsequent pregnancy test is negative.
• Ability of reading, comprehending and finishing trial questionnaires and record, including VAS (Visual Analogue Scale) question.
• Before subject registration, written informed consent must be given according to local regulations.

Exclusion Criteria:

• Pregnant women without morning sickness.
• Presence of gastrointestinal tract obstruction or electrolyte imbalance.
• Any history of central nervous system disease(e.g. Primary brain tumour, seizure not controlled with standard medical therapy, brain metastases or history of stroke).
• Contraindication of glucocorticoid:1.Infection of virus, bacteria or fungus uncontrolled by antibiotics; 2.Active stomach or duodenum ulcer; 3.Severe hypertension, atherosclerosis, diabetes; 4.Osteoporosis;5.Corneal ulcer; 6.Pregnancy; 7.Reparative phase of trauma, operation or fraction; 8.Hypercortisolism; 9.Severe mental disorder or epilepsy; 10.Inadequate cardiac or renal function.
• Mental disability or severe emotional or mental disorder.
• Active infection(e.g. pneumonia, hepatitis) or any uncontrolled disease(e.g.diabetic ketoacidosis) that may affect study outcome or expose patients to unnecessary risk.
• Usage of any illicit drug, including medical marijuana or alcohol abusing(China drug dependence criteria).
• Treatment of unapproved medicine in the previous 4 weeks.
• Concomitant therapy of psychotropic medicine such as olanzapine.
• Hypersensitivity history towards Aprepitant, 5-HT3 receptor antagonist or dexamethasone.
• Previous treatment of Aprepitant.
• Unable to swallow capsules.
• Main researchers considered that the patient is unsuited to the trial.
• Unable or unwilling to follow research programme.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Palonosetron/Dexamethasone/Aprepitant	Drug: Aprepitant; Aprepitant is manufactured by Merck & Co. for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting. It was approved by the FDA in 2003; Drug: Palonosetron; Palonosetron is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is used for the control of delayed CINV-nausea and vomiting and there are tentative data to suggest that it may be more effective than granisetron.; Drug: Dexamethasone; Dexamethasone is a type of corticosteroid medication. It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, and along with antibiotics in tuberculosis.
PLACEBO_COMPARATOR: Palonosetron/Dexamethasone/Placebo	Drug: Palonosetron; Palonosetron is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is used for the control of delayed CINV-nausea and vomiting and there are tentative data to suggest that it may be more effective than granisetron.; Drug: Dexamethasone; Dexamethasone is a type of corticosteroid medication. It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, and along with antibiotics in tuberculosis.; Drug: Placebo Oral Tablet; In the current clinical trial, placebo oral tablet is provided as a substance for Aprepitant with no active therapeutic effect.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate during the overall phase	The proportion of patients without emesis episodes or rescue medication use during the overall phase (0-120 h)	Up to 1-2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate in the acute phase	The proportion of patients without emesis episodes or rescue medication use during the acute phase (0-24h)	Up to 1-2 months
Complete response rate in the delayed phase	The proportion of patients without emesis episodes or rescue medication use during the delayed phase (25-120 h)	Up to 1-2 months
No vomiting rate in the acute phase, delayed phase and overall phase	The proportion of no vomiting (no vomiting or retching episodes) in the acute phase, delayed phase and overall phase	Up to 1-2 months
Affection caused by CINV reported by patients		Up to 1-2 months
Effects of CINV on daily life		Up to 1-2 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Publications and helpful links

General Publications

• Wang DS, Hu MT, Wang ZQ, Ren C, Qiu MZ, Luo HY, Jin Y, Fong WP, Wang SB, Peng JW, Zou QF, Tan Q, Wang FH, Li YH. Effect of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Women: A Randomized Clinical Trial. JAMA Netw Open. 2021 Apr 1;4(4):e215250. doi: 10.1001/jamanetworkopen.2021.5250.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 4, 2015
• Primary Completion (ACTUAL): March 31, 2020
• Study Completion (ACTUAL): June 1, 2020

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: September 13, 2018
• First Posted (ACTUAL): September 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Nausea; Vomiting; Gastrointestinal Neoplasms; Digestive System Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; 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; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Palonosetron; Aprepitant
• Other Study ID Numbers: Aprepitant-CINV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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