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) .

Study Overview

• Status: Unknown
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Dexamethasone; Drug: 5-HT3 antagonists; Drug: Thalidomide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 880
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiujuan Qu, PhD. M.D.; Phone Number: 024-83282542; Email: qu_xiujuan@hotmail.com
• Study Contact Backup: Name: Lingyun Zhang, PhD. M.D.; Phone Number: 024-83282312; Email: zhangly1105@126.com

Study Locations

• China
  • Anshan, China
    • Not yet recruiting
    • Central Hospital of Anshan City
    • Contact: Chuanchun Leng
    • Sub-Investigator: Chuanchun Leng
  • Benxi, China
    • Not yet recruiting
    • Benxi Central Hospital
    • Contact: Tiejun Chen
    • Sub-Investigator: Tiejun Chen
  • Chaoyang, China
    • Not yet recruiting
    • Chaoyang Central Hospital
    • Contact: Xiujie Cui
    • Sub-Investigator: Xiujie Cui
  • Dalian, China
    • Not yet recruiting
    • Zhongshan Hospital
    • Contact: Xuening Ji, M.D.
    • Sub-Investigator: Xuening Ji
    • Sub-Investigator: Gang Wang
    • Sub-Investigator: Tong Zhao
  • Panjin, China
    • Not yet recruiting
    • Liaohe Oilfield General Hospital
    • Contact: Qiang Chen
    • Sub-Investigator: Qiang Chen
  • Heilongjiang
    • Haerbin, Heilongjiang, China
      • Not yet recruiting
      • cancer hospital of Haerbin Medical University
      • Contact: Jin Wu, M.D.
  • Jilin
    • Siping, Jilin, China
      • Not yet recruiting
      • Siping City Cancer Hospital
      • Contact: Zhuohui Qu
      • Sub-Investigator: Zhuohui Qu
  • Liaoning
    • Anshan, Liaoning, China
      • Not yet recruiting
      • Anshan Hospital of First Hospital of China Medical University
      • Contact: Mingran Sun, PhD.M.D.
      • Sub-Investigator: Mingran Sun
    • Anshan, Liaoning, China
      • Not yet recruiting
      • Anshan Tumor Hospital
      • Contact: Xiuna Zhang, M.D.
      • Sub-Investigator: Xiuna Zhang
      • Sub-Investigator: Jinfang Lv
      • Sub-Investigator: Fugang When
      • Sub-Investigator: Li Man
    • Dalian, Liaoning, China
      • Not yet recruiting
      • Central hospital of Dalian
      • Contact: Wei Huo
      • Sub-Investigator: Wei huo
      • Sub-Investigator: Min Zhong
      • Sub-Investigator: Liangwei Yin
    • Dalian, Liaoning, China
      • Not yet recruiting
      • Second Affiliated Hospital of Dalian Medical University
      • Contact: Zhaoxia Dai, M.D.
      • Sub-Investigator: Zhaoxia Dai
      • Sub-Investigator: Jun Chen
    • Dalian, Liaoning, China
      • Not yet recruiting
      • The Fifth Hospital of Dalian City
      • Contact: Jilai Bian
      • Sub-Investigator: Jilai Bian
    • Dalian, Liaoning, China
      • Not yet recruiting
      • The First Affiliated Hospital of Dalian Medical University
      • Contact: Jiwei Liu, PhD;M.D.
      • Sub-Investigator: Jiwei Liu
    • Dalian, Liaoning, China
      • Not yet recruiting
      • Zhuanghe central hospital
      • Contact: Huali Tang
      • Sub-Investigator: Huali Tang
    • Fushun, Liaoning, China
      • Recruiting
      • Fushun central hospital
      • Contact: Li Ning
      • Sub-Investigator: Li Ning
    • Fushun, Liaoning, China
      • Not yet recruiting
      • General Hospital of Mining Bureau
      • Contact: Yuyang Zhang
      • Sub-Investigator: Yuyang Zhang
    • Jinzhou, Liaoning, China
      • Not yet recruiting
      • Jinzhou Central Hospital
    • Jinzhou, Liaoning, China
      • Not yet recruiting
      • The First Hospital of Liaoning Medical University
      • Contact: Zhitu Zhu
      • Sub-Investigator: Zhitu Zhu
    • Liaoyang, Liaoning, China
      • Not yet recruiting
      • Chinese Medicine Hospital of Liaoyang county
      • Contact: Haifeng Liu, M.D.
      • Sub-Investigator: Haifeng Liu
    • Liaoyang, Liaoning, China
      • Not yet recruiting
      • Liaoyang Central Hospital
      • Contact: Jian Zhang, M.D.
    • Liaoyang, Liaoning, China
      • Not yet recruiting
      • Petrochemical General Hospital of Liaoyang city
      • Contact: Hao Chen
    • Panjin, Liaoning, China
      • Not yet recruiting
      • Panjin Central Hospital
      • Contact: Junwei Zhang
      • Sub-Investigator: Junwei Zhang
      • Sub-Investigator: Zhichang Sun
      • Sub-Investigator: Yu Jiang
      • Sub-Investigator: Qinghua Gao
    • Shengyang, Liaoning, China
      • Not yet recruiting
      • Chest Hospital of Shenyang City
      • Contact: Yinyin Li
      • Sub-Investigator: Yinyin Li
    • Shenyang, Liaoning, China, 110004
      • Not yet recruiting
      • Shengjing Hospital of China Medical University
      • Contact: Huawei Zou, M.D.
      • Sub-Investigator: Huawei Zou
      • Sub-Investigator: Rong Wu
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • General Hospital of Shenyang Military Region
      • Sub-Investigator: Zhendong Zheng
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • Liaoning Tumor Hospital & Institute
      • Contact: Yu Tang, M.D.
      • Sub-Investigator: Yu Tang
    • Shenyang, Liaoning, China
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: Yunpeng Liu, M.D.;Ph.D.
      • Principal Investigator: Yunpeng Liu
      • Sub-Investigator: Xiujuan Qu
      • Sub-Investigator: Lingyun Zhang
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • the People'S Hospital
      • Contact: Lijie He, M.D.
      • Sub-Investigator: Lijie He
    • Tieling, Liaoning, China
      • Not yet recruiting
      • Tieling city Central Hospital
      • Contact: Huijun Zhang
      • Sub-Investigator: Huijun Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 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;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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Yunpeng Liu
• Investigators: Principal Investigator: Yunpeng Liu, PhD. M.D., China Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2018
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: May 30, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 25, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Thalidomide; Chemotherapy-induced Nausea and Vomiting; cisplatin
• 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; Dexamethasone; Thalidomide; Palonosetron; Serotonin 5-HT3 Receptor Antagonists
• Other Study ID Numbers: CLOG1801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No