The Efficacy and Safety of Thalidomide in Preventing CINV Induced by Cisplatin-containing Chemotherapy

Study Overview
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Brief Summary
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This is a pragmatic randomized, multi-center, open-label randomized clinical trial, aimed to evaluate efficacy and safety of thalidomide in improving prevention of chemotherapy-induced delayed nausea and vomiting (CINV) in chemotherapy-naive patients after multi-cycle cisplatin-containing highly emetogenic chemotherapy (HEC) .

Detailed Description
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This is a pragmatic randomized, multi-center, open-label randomized clinical trial, aimed to evaluate efficacy and safety of thalidomide in improving prevention of chemotherapy-induced delayed nausea and vomiting (CINV) in chemotherapy-naive patients after multi-cycle cisplatin-containing highly emetogenic chemotherapy (HEC) . A total of 880 patients are planned to be enrolled into the study. Chemotherapy-naïve patients treated with multi-cycle cisplatin-containing chemotherapy will be randomized into two groups(thalidomide group and control group), and be treated with Thalidomide+5-hydroxytryptamine receptor(5-HT3) antagonist +Dexamethasone (Thalidomide group) or 5-HT3 antagonist + Dexamethasone(control group), respectively. The primary end point is no nausea rate in delayed phase of the first cycle chemotherapy, and the secondary end points include the complete response rate of vomiting in acute,delayed and overall period; no nausea rate in acute and overall phase; anorexia score, fatigue score and sedation score assessed by VAS ; safety and quality of life (QOL) during multi-cycle chemotherapy.

Official Title
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The Efficacy and Safety of Thalidomide in Preventing Multi-cycle, Cisplatin-containing CINV: a Pragmatic Randomized Open-label Clinical Trial

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Thalidomide
* Drug: Dexamethasone
* Drug: 5-HT3 antagonists


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;the patients and their couples should receive contraception for at least 3 years after their last dosage of thalidomide. Cancer patients scheduled to receive chemotherapy containing a 50 mg/m2 or higher dose of cisplatin for 4-6 cycles Exclusion Criteria: Diabetic patients Pregnant or lactated women Patient with history of severe thrombosis Concomitant radiotherapy Known hypersensitivity yo 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 Cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone (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: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Palonosetron 0.25 mg intravenously on day 1; or 1st-generation 5-HT3 antagonists (used as clinal routine) on day 1-3; Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4. | Drug: Dexamethasone<br>* Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4<br>Drug: 5-HT3 antagonists<br>* Palonosetron 0.25 mg intravenously on day 1; or 1st-generation 5-HT3 antagonists (used as clinal routine) on day 1-3<br>* Other names: Palonosetron, or 1st-generation 5-HT3 antagonists;|
| Experimental: Thalidomide group<br>Thalidomide 100 mg by mouth twice a day on days 1-5; Palonosetron 0.25 mg intravenously on day 1; or 1st-generation 5-HT3 antagonists (used as clinal routine) on day 1-3; Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4. | Drug: Thalidomide<br>* Thalidomide (Thalidomide Oral Product)100 mg by mouth twice a day on days 1-5 after chemotherapy .<br>Drug: Dexamethasone<br>* Dexamethasone 12 mg by mouth or intravenously before chemotherapy on day 1 and 8 mg on days 2-4<br>Drug: 5-HT3 antagonists<br>* Palonosetron 0.25 mg intravenously on day 1; or 1st-generation 5-HT3 antagonists (used as clinal routine) on day 1-3<br>* Other names: Palonosetron, or 1st-generation 5-HT3 antagonists;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No nausea （self report sclae VAS=0）rate in delayed phase (Days2-7) in the first cycle chemotherapy | The rate of no nausea on Day 2-7 in the first chemotherapy cycle (each cycle is 21 days). The no nausea is defined as score zero with a self-report measure scale,the visual analogue (VAS) scale (0,no symptom, 10, most severely). | Day 2-7 in the first chemotherapy cycle(each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No nausea rates （VAS=0）for delayed phases (Days2-7) during 2nd to 4th or 6th chemotherapy cycle,respectively. | The rates of no nausea on day 2-7 in 2nd-4th or 6th cycle (each cycle is 21 days). The no nausea is defined as score zero with a self-report measure scale,the visual analogue (VAS) scale (0,no symptom, 10, most severely). | Day 2-7 in each chemotherapy cycle (each cycle is 21 days) | 
| The complete response rates of vomiting (no emetic episode and no rescue) in acute (Day1),delayed(Day2-7), and overall phase(Day 1-7) during 1st to 4th or 6th cycle, respectively. | The rates of no emetic episode and no rescue in acute(Day1),delayed(Day2-7), and overall phase(Day 1-7) during 1st to 4th or 6th cycle, respectively.(each cycle is 21 days). An emetic episode is defined as one occurrence of vomiting or a sequence of occurrences in close succession not relieved by a rest period of at least 1 min; any number of episodes of retching in a 5-minute period; or an episode of retching of , 5 minutes combined with vomiting not relieved in a 1-minute period. | Day 1-7 in 4-6 cycles(each cycle is 21 days) | 
| The rate of no anorexia (VAS=0) and score of anorexia (assessed by VAS) in Day1-7 during 1st-4th or 6th cycle chemotherapy | The rate of no anorexia (VAS=0) and score of anorexia assessed by VAS in multi-cycle chemotherapy. Anorexia score is evaluated with VAS (0,no symptom, 10, most severely) | Day 1-7 in each cycle(each cycle is 21 days) | 
| The score of fatigue by VAS in day1-7 in1st to 4th or 6th chemotherapy cycle,respectively. | The score of fatigue by self-report scale VAS in day1-7 in1st to 4th or 6th chemotherapy. fatigue is evaluated with self-report scale VAS (0,no symptom, 10, most severely） | Day 1-7 in each cycle(each cycle is 21 days) | 
| The score of sedation(by self-report VAS) in day 1-7 in each cycle | The score of sedation(by self-report VAS) in day 1-7 in each cycle, respectively.Sedation is evaluated with self-report VAS (0,no symptom, 10, most severely） | Day 1-7 in each cycle(each cycle is 21 days) | 
| Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 in multi-cycle chemotherapy | Number of participants with Treatment-Related Adverse Events as assessed by CTCAE v4.0, in 4-6 cycles (each cycle is 21 days). | Day 1-21 in each cycle(each cycle is 21 days) during 4-6 chemotherapy cycles (each cycle is 21 days) | 
| The quality of life scores (evaluated with Functional Living Index-Emesis (FLIE) questionnaire) of patients when receiving multi-cycle chemotherapy | The change of quality of life scores from baseline of patients (before chemotherapy) to D8 after chemotherapy in each cycle (each cycle is 21 days). The quality of life are evaluated with Functional Living Index-Emesis (FLIE) questionnaire. | Day 1-8 in each cycle(each cycle is 21 days) during 4-6 chemotherapy cycles. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalidomide, Chemotherapy-induced Nausea and Vomiting, cisplatin