Efficacy of Thalidomide in Preventing Chemotherapy-induced Delayed Nausea and Vomiting

Efficacy of Thalidomide in Preventing Chemotherapy-induced Delayed Nausea and Vomiting From Highly Emetogenic Chemotherapy: a Randomized, Multicenter, Double-blind, Placebo-controlled Phase III Trial

This study was aimed to evaluate efficacy and tolerability of thalidomide in improving prevention of chemotherapy-induced delayed nausea and vomiting in chemotherapy-naive patients after highly emetogenic chemotherapy.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Thalidomide; Drug: Palonosetron and Dexamethasone; Drug: Placebo for thalidomide

Detailed Description

This is a prospective, randomized, multi-center, double-blind, placebo-controlled clinical trial, aimed to evaluate efficacy and tolerability of thalidomide in improving prevention of chemotherapy-induced delayed nausea and vomiting (CINV) in chemotherapy-naive patients after highly emetogenic chemotherapy(HEC) (cisplatin-based regimen or cyclophosphamide combination with doxorubicin/epirubicin). A total of 820 patients are planned to be enrolled into the study. Patients treating with highly emetogenic chemotherapy will be randomized into two groups, and be treated with Thalidomide+ Palonosetron+ Dexamethasone or Placebo + Palonosetron+ Dexamethasone, respectively. The primary end point is complete response rate (CRR) for delayed CINV, and the secondary end points include the safety and quality of life (QOL).

• Study Type: Interventional
• Enrollment (Actual): 642
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Anshan, Liaoning, China
      • Anshan Tumor Hospital
    • Dalian, Liaoning, China
      • The First Affiliated Hospital of Dalian Medical University
    • Dalian, Liaoning, China
      • Second Affiliated Hospital of Dalian Medical University
    • Jinzhou, Liaoning, China
      • The First Hospital of Liaoning Medical University
    • Liaoyang, Liaoning, China
      • Liaoyang Central Hospital
    • Liaoyang, Liaoning, China
      • Petrochemical General Hospital of Liaoyang city
    • Liaoyang, Liaoning, China
      • Third People's hospital Liaoyang
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China
      • General Hospital of Shenyang Military Region
    • Shenyang, Liaoning, China
      • Liaoning Tumor Hospital & Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18y ≤Age≤70y
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Histologically confirmed solid neoplasm
• No prior chemotherapy
• Laboratory test must meet the following criteria: hemoglobin (HGB) ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥85×109/L, creatinine clearance rate (CCr) ≥60ml/min, total bilirubin (TBil) ≤1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 UNL (For patients with liver metastasis, the AST/ALT must be ≤5.0 UNL), blood glucose ≤11.1 mmol/L
• Life expectancy of at least 12 weeks
• Signed informed consent
• For women with child bearing potential, a negative serum or urine pregnancy test result should be obtained before enrollment
• Cancer patients scheduled to receive HEC regimen. The HEC regimen was defined as chemotherapy containing a 50 mg/m2 or higher dose of cisplatin, or cyclophosphamide combination with doxorubicin/epirubicin

Exclusion Criteria:

• Diabetic patients
• Pregnant or lactated women
• Patient with history of thrombosis
• Concomitant radiotherapy
• Known hypersensitivity to thalidomide, palonosetron, or dexamethasone.
• Concurrent administration of any other drug which affect antiemetic effect evaluation such as proton pump inhibitor, H2 blocker, amifostine, sedative drugs
• CHOP regiment or taxanes-based regiment
• Existing emesis within 24 hours before chemotherapy administration
• Symptomatic brain metastasis or suspected clinical brain metastasis
• Serious uncontrolled systemic illness or medical condition: congestive heart failure, unstable angina, history of documented myocardial infarction within 6 months, uncontrolled hypertension and high risk uncontrollable arrhythmias; Obvious neurological or mental abnormalities including mental disorder, epileptic dementia, which affect compliance; Uncontrolled acute infections; Uncontrolled peptic ulcer or other contraindication for corticosteroid therapy.
• Inability to take or absorb oral medicine
• Concurrent administration of any other investigational drug, or have been enrolled in other clinical trial with investigational drug treatment within the 30 days of start of study treatment
• Unsuitable for the study or other chemotherapy determined by investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thalidomide Group; Thalidomide 100 mg by mouth twice a day on days 1-5; Palonosetron 0.25 mg intravenously on day 1; Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4; cycle 1.	Drug: Thalidomide; 100 mg by mouth twice a day on days 1-5 after chemotherapy, cycle 1; Drug: Palonosetron and Dexamethasone; Palonosetron 0.25 mg intravenously on day 1; Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4; cycle 1.
Placebo Comparator: Placebo Group; Placebo (for Thalidomide) tablet 100 mg by mouth twice a day on days 1-5; Palonosetron 0.25 mg intravenously on day 1; Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4; cycle 1.	Drug: Palonosetron and Dexamethasone; Palonosetron 0.25 mg intravenously on day 1; Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4; cycle 1.; Drug: Placebo for thalidomide; Placebo tablet manufactured to mimic Thalidomide 25 mg tablet 100 mg by mouth twice a day on days 1-5 after chemotherapy , cycle 1; Other Names: Placebo tablet for thalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
complete response rate (CRR) for delayed CINV	120 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse Events	Up to 3 weeks
quality of life	up to 7 days

Collaborators and Investigators

• Sponsor: China Medical University, China
• Collaborators: General Hospital of Shenyang Military Region; Shengjing Hospital; Liaoning Tumor Hospital & Institute; The First Affiliated Hospital of Dalian Medical University; The Second Affiliated Hospital of Dalian Medical University; Anshan Tumor Hospital; Liaoyang Central Hospital; The First Hospital of Liaoning Medical University; Third People's hospital Liaoyang; Petrochemical General Hospital of Liaoyang city
• Investigators: Principal Investigator: Yunpeng Liu, MD., PhD, China Medical University, China

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: July 23, 2014
• First Submitted That Met QC Criteria: July 27, 2014
• First Posted (Estimate): July 29, 2014

Study Record Updates

• Last Update Posted (Estimate): August 24, 2016
• Last Update Submitted That Met QC Criteria: August 23, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: prevention; solid tumor; thalidomide; chemotherapy-induced delayed nausea and vomiting
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Serotonin Agents; Serotonin Antagonists; Leprostatic Agents; Serotonin 5-HT3 Receptor Antagonists; Dexamethasone; Thalidomide; Palonosetron
• Other Study ID Numbers: CLOG1302