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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: Thalidomide
* Drug: Placebo for thalidomide
* Drug: Palonosetron and Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Thalidomide Group<br>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<br>* 100 mg by mouth twice a day on days 1-5 after chemotherapy, cycle 1<br>Drug: Palonosetron and Dexamethasone<br>* 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.<br>|
| Placebo Comparator: Placebo Group<br>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: Placebo for thalidomide<br>* Placebo tablet manufactured to mimic Thalidomide 25 mg tablet 100 mg by mouth twice a day on days 1-5 after chemotherapy , cycle 1<br>* Other names: Placebo tablet for thalidomide;Drug: Palonosetron and Dexamethasone<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumor, chemotherapy-induced delayed nausea and vomiting, thalidomide, prevention