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出境医 / 临床实验 / Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma (NTNC)

Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma (NTNC)

Study Description
Brief Summary:
To verify the role of nab-paclitaxel in neoadjuvant therapy for esophageal squamous cell carcinoma, the investigators designed a prospective, randomized, controlled , multicente phase II trial, to investigate the efficacy and safety of nab-paclitaxel combined with cisplatin as neoadjuvant therapy followed by surgery versus surgery alone for esophageal squamous cell carcinoma.

Condition or disease Intervention/treatment Phase
Esophageal Squamous Cell Carcinoma Drug: Nab-paclitaxel and Cisplatin Procedure: surgery Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effectiveness and Safety of Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin Followed by Surgery Versus Surgery Alone for Locally Advanced Esophageal Squamous Cell Carcinoma
Actual Study Start Date : April 24, 2019
Estimated Primary Completion Date : June 24, 2026
Estimated Study Completion Date : December 24, 2026
Arms and Interventions
Arm Intervention/treatment
Experimental: Neo-adjuvant chemotherapy group

cisplatin and nab-paclitaxel: Nab-paclitaxel, 125mg/m(2), d1,d8, Cisplatin, 75mg/m(2), d1, 3 week, 2 cycles.

Surgery:

4-6weeks after Neo-adjuvant chemotherapy

Drug: Nab-paclitaxel and Cisplatin
Nab-paclitaxel,125mg/m(2), d1,d8, Cisplatin,75mg/m(2), d1, 3 week, 2 cycles.

Procedure: surgery
surgery

Active Comparator: Surgery alone
Surgery alone
Procedure: surgery
surgery

Outcome Measures
Primary Outcome Measures :
  1. OS [ Time Frame: up to 5 years ]
    Overall survival,From date of randomization until death due to any cause


Secondary Outcome Measures :
  1. OS rate [ Time Frame: 1 year,3years,5years ]
    Overall survival rate

  2. DFS rate [ Time Frame: 1 year,3years,5years ]
    Disease free survival rate

  3. R0 resection rate [ Time Frame: within 4 weeks following the operation ]
    R0 resection rate

  4. Down-staging rate [ Time Frame: within 6 weeks following the last dose of chemotherapy ]
    Down-staging rate

  5. Rate of Operative Complications [ Time Frame: within 4 weeks following the operation ]
  6. Rate of Adverse Event [ Time Frame: up to 6 weeks after the last dose of chemotherapy ]
    Incidence of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ranges from 18 to 75 years
  • Radiographically, histologically or/and cytologically diagnosed resectable locally advanced middle-lower esophageal squamous cell carcinoma without distant metastasis,cT1N1M0 or T2-3N0-1M0(according to UICC esophageal cancer TNM staging system 8th edition)
  • Enhanced CT showed the presence of potentially resectable lesions. Resectability features included no evidence of mediastinal infiltration, No evidence of tracheobronchial fistula or tumor entry into the airway
  • Have not previously received systemic antitumor therapy for esophageal squamous cell carcinoma (Including radiotherapy, chemotherapy, targeted therapy, immunotherapy)
  • ECOG performance status 0-1
  • Expected survival more than 6 months
  • No contraindications in the organ function tests before surgery
  • The laboratory test meet the following requirements:

Bone marrow function: neutrophils ≥ 1.5×10(9)/L, platelets ≥ 100×10(9)/L, hemoglobin ≥ 90 g/L Liver function:Total bilirubin ≤ 1.5x ULN;AST and ALT) ≤ 2.5x ULN Renal function:Cr ≤ 1.5x ULN,Ccr ≥ 55 ml/min Coagulation function:INR≤1.5×ULN, PT≤1.5ULN, APTT within the normal range

  • Female patients of child-bearing age agree to take effective contraceptive measures during the study period and 6 months after reseach completion;Pregnancy tests in serum or urine must be negative 7 days prior to study enrollment;Non-lactating patients;male patients agree to take effective contraceptive measures during the study period and 6 months after reseach completion
  • Not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver)
  • Not participating in other clinical trials 4 weeks before the treatment
  • The patient has good compliance with the planned treatment, understands the research process of the study and signs a written informed consent form.

Exclusion Criteria:

  • Histological confirmation of esophageal adenocarcinoma
  • with distant metastasis, without radical resection (stage IV)
  • Ever administrated with other drugs(including TCM drugs) before the recruitment, or no guarantee of progress according to the study requirement after recruitment
  • Grade 2 or above peripheral neuropathy or hemorrhage according to NCI CTCAE 4.03
  • Combined with severe cardiovascular disease, including hypertension that cannot be controlled by medical treatment(BP≥160/95mmHg), unstable angina, a history of myocardial infarction in the past 6 months,Congestive heart failure>NYHA grade II, severe arrhythmia, pericardial effusion, etc.
  • Combined with severe ADH abnormal secretion syndrome, poorly controlled diabetes: more than 40 units of insulin per day need to be continuously administered; or 40 units of insulin per day for continuous use or not used, but fasting blood glucose is still above 14mmol / L, HbA1c above 9.0
  • Long-term use of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues for more than 6 months,small doses of warfarin (≤1mg / day) or aspirin (≤100mg / day) for prevention purposes are not included
  • Major surgery within 4 weeks prior to enrollment, or surgical wounds have not fully healed
  • Operation can not use the stomach instead of esophageal cancer to reconstruct the digestive tract due to previous operation
  • Severe infection within 1 week prior to the start of study, requiring intravenous antibiotics, antifungal or antiviral therapy
  • Known to be allergic, highly sensitive or intolerable to research-related drugs or excipient
  • In the past 5 years, there were other malignant tumors, melanoma skin cancer or ervical carcinoma in situ were excepted
  • Any indicator shows chemotherapy and surgery contraindications
  • Women who are pregnant or lactating
  • The investigator determined that unable to complete the study due to medical, social, or psychological reasons or were unable to sign valid informed consent
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Junfeng Liu, PhD 13931152296 liujf@hbmu.edu

Locations
Layout table for location information
China, Hebei
Jun Feng Liu Recruiting
Shijiazhuang, Hebei, China, 050011
Contact: Jun Feng Liu, PhD    13931152296      
Sponsors and Collaborators
Hebei Medical University Fourth Hospital
Tracking Information
First Submitted Date  ICMJE May 18, 2019
First Posted Date  ICMJE May 28, 2019
Last Update Posted Date August 15, 2019
Actual Study Start Date  ICMJE April 24, 2019
Estimated Primary Completion Date June 24, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
OS [ Time Frame: up to 5 years ]
Overall survival,From date of randomization until death due to any cause
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
  • OS rate [ Time Frame: 1 year,3years,5years ]
    Overall survival rate
  • DFS rate [ Time Frame: 1 year,3years,5years ]
    Disease free survival rate
  • R0 resection rate [ Time Frame: within 4 weeks following the operation ]
    R0 resection rate
  • Down-staging rate [ Time Frame: within 6 weeks following the last dose of chemotherapy ]
    Down-staging rate
  • Rate of Operative Complications [ Time Frame: within 4 weeks following the operation ]
  • Rate of Adverse Event [ Time Frame: up to 6 weeks after the last dose of chemotherapy ]
    Incidence of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
  • OS rate [ Time Frame: 1 year,3years,5years ]
    Overall survival rate
  • DFS rate [ Time Frame: 1 year,3years,5years ]
    Disease free survival rate
  • R0 resection rate [ Time Frame: within 4 weeks following the operation ]
    R0 resection rate
  • Down-staging rate [ Time Frame: within 6 weeks following the last dose of chemotherapy ]
    Down-staging rate
  • Operative complications [ Time Frame: within 4 weeks following the operation ]
    Operative complications
  • Adverse Event [ Time Frame: up to 6 weeks after the last dose of chemotherapy ]
    Adverse events Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin for Locally Advanced Esophageal Squamous Cell Carcinoma
Official Title  ICMJE The Effectiveness and Safety of Neoadjuvant Therapy With Nab-paclitaxel and Cisplatin Followed by Surgery Versus Surgery Alone for Locally Advanced Esophageal Squamous Cell Carcinoma
Brief Summary To verify the role of nab-paclitaxel in neoadjuvant therapy for esophageal squamous cell carcinoma, the investigators designed a prospective, randomized, controlled , multicente phase II trial, to investigate the efficacy and safety of nab-paclitaxel combined with cisplatin as neoadjuvant therapy followed by surgery versus surgery alone for esophageal squamous cell carcinoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Esophageal Squamous Cell Carcinoma
Intervention  ICMJE
  • Drug: Nab-paclitaxel and Cisplatin
    Nab-paclitaxel,125mg/m(2), d1,d8, Cisplatin,75mg/m(2), d1, 3 week, 2 cycles.
  • Procedure: surgery
    surgery
Study Arms  ICMJE
  • Experimental: Neo-adjuvant chemotherapy group

    cisplatin and nab-paclitaxel: Nab-paclitaxel, 125mg/m(2), d1,d8, Cisplatin, 75mg/m(2), d1, 3 week, 2 cycles.

    Surgery:

    4-6weeks after Neo-adjuvant chemotherapy

    Interventions:
    • Drug: Nab-paclitaxel and Cisplatin
    • Procedure: surgery
  • Active Comparator: Surgery alone
    Surgery alone
    Intervention: Procedure: surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 23, 2019)
202
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 24, 2026
Estimated Primary Completion Date June 24, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ranges from 18 to 75 years
  • Radiographically, histologically or/and cytologically diagnosed resectable locally advanced middle-lower esophageal squamous cell carcinoma without distant metastasis,cT1N1M0 or T2-3N0-1M0(according to UICC esophageal cancer TNM staging system 8th edition)
  • Enhanced CT showed the presence of potentially resectable lesions. Resectability features included no evidence of mediastinal infiltration, No evidence of tracheobronchial fistula or tumor entry into the airway
  • Have not previously received systemic antitumor therapy for esophageal squamous cell carcinoma (Including radiotherapy, chemotherapy, targeted therapy, immunotherapy)
  • ECOG performance status 0-1
  • Expected survival more than 6 months
  • No contraindications in the organ function tests before surgery
  • The laboratory test meet the following requirements:

Bone marrow function: neutrophils ≥ 1.5×10(9)/L, platelets ≥ 100×10(9)/L, hemoglobin ≥ 90 g/L Liver function:Total bilirubin ≤ 1.5x ULN;AST and ALT) ≤ 2.5x ULN Renal function:Cr ≤ 1.5x ULN,Ccr ≥ 55 ml/min Coagulation function:INR≤1.5×ULN, PT≤1.5ULN, APTT within the normal range

  • Female patients of child-bearing age agree to take effective contraceptive measures during the study period and 6 months after reseach completion;Pregnancy tests in serum or urine must be negative 7 days prior to study enrollment;Non-lactating patients;male patients agree to take effective contraceptive measures during the study period and 6 months after reseach completion
  • Not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver)
  • Not participating in other clinical trials 4 weeks before the treatment
  • The patient has good compliance with the planned treatment, understands the research process of the study and signs a written informed consent form.

Exclusion Criteria:

  • Histological confirmation of esophageal adenocarcinoma
  • with distant metastasis, without radical resection (stage IV)
  • Ever administrated with other drugs(including TCM drugs) before the recruitment, or no guarantee of progress according to the study requirement after recruitment
  • Grade 2 or above peripheral neuropathy or hemorrhage according to NCI CTCAE 4.03
  • Combined with severe cardiovascular disease, including hypertension that cannot be controlled by medical treatment(BP≥160/95mmHg), unstable angina, a history of myocardial infarction in the past 6 months,Congestive heart failure>NYHA grade II, severe arrhythmia, pericardial effusion, etc.
  • Combined with severe ADH abnormal secretion syndrome, poorly controlled diabetes: more than 40 units of insulin per day need to be continuously administered; or 40 units of insulin per day for continuous use or not used, but fasting blood glucose is still above 14mmol / L, HbA1c above 9.0
  • Long-term use of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues for more than 6 months,small doses of warfarin (≤1mg / day) or aspirin (≤100mg / day) for prevention purposes are not included
  • Major surgery within 4 weeks prior to enrollment, or surgical wounds have not fully healed
  • Operation can not use the stomach instead of esophageal cancer to reconstruct the digestive tract due to previous operation
  • Severe infection within 1 week prior to the start of study, requiring intravenous antibiotics, antifungal or antiviral therapy
  • Known to be allergic, highly sensitive or intolerable to research-related drugs or excipient
  • In the past 5 years, there were other malignant tumors, melanoma skin cancer or ervical carcinoma in situ were excepted
  • Any indicator shows chemotherapy and surgery contraindications
  • Women who are pregnant or lactating
  • The investigator determined that unable to complete the study due to medical, social, or psychological reasons or were unable to sign valid informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Junfeng Liu, PhD 13931152296 liujf@hbmu.edu
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03964753
Other Study ID Numbers  ICMJE HebeiJLiu
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party LiuJunFeng, Hebei Medical University Fourth Hospital
Study Sponsor  ICMJE Hebei Medical University Fourth Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Hebei Medical University Fourth Hospital
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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