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

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

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) .

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.

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