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Apatinib in the Treatment of Recurrence or Metastasis of Esophageal Cancer

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ClinicalTrials.gov Identifier: NCT03913182
Recruitment Status : Active, not recruiting
First Posted : April 12, 2019
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
Zhiang Li, Shanghai Chest Hospital

Brief Summary:
It was difficult to obtain clinical benefits through traditional chemotherapy and radiotherapy for the patients who have recurrence or metastasis tumor even though they have received first-line chemotherapy or combined radiotherapy before, but failed.The aim of this study was to evaluate the safety and efficacy of apatinib, an anti-angiogenesis drug, in the treatment of patients with advanced esophageal squamous cell carcinoma who had recurrence or metastasis after radical resection

Condition or disease Intervention/treatment Phase
Esophageal Squamous Cell Carcinoma Apatinib Recurrence Metastasis Drug: apatinib Phase 2

Detailed Description:

Esophageal cancer is a common malignant tumor in China and its prognosis is poor. Its main treatment methods include surgery, radiotherapy and chemotherapy. However, the 5-year survival rate of esophageal cancer after operation is only about 40%. The main cause of treatment failure is postoperative recurrence and metastasis.The 2-year recurrence rate of esophageal cancer after radical operation was 50%, the median recurrence time was about 10 months and the 2-year survival rate was less than 15% for these patients.For patients with local recurrence, endoscopic submucosal resection, salvage resection and radiotherapy could be chosen. Palliative chemotherapy is another important method for patients with recurrence or metastasis who are not suitable for surgery or radiotherapy.Cisplatin combined with fluorouracil is a usually used first-line chemotherapy regimen, but the response rate is less than 30% and the median survival time is only about 6~10 months.There is no standard second-line treatment for patients who have failed first-line treatment. Over the past decade, the second-line treatment for esophageal cancer is mostly phase I and II studies. The reported objective remission rate(ORR) ranges from 2.8% to 45%, the median progression-free survival (PFS) ranges from 1.2 to 5.2 months and the median overall survival (OS) ranges from 3.7 to 11.4 months.Although some studies have shown that taxus-based second-line chemotherapy can bring a certain degree of remission to patients, irinotecan, gemcitabine and oxaliplatin can also be used as the second-line chemotherapy options for these patients, but the overall efficiency is low and disease progression occurs quickly.The median survival time of esophageal stent, nasal feeding nutrition support and gastrostomy is only 6 months, and the 1-year survival rate is generally less than 5%.The previous treatment options are few and the therapeutic effect is poor for the patients with locally advanced esophageal cancer who have received neoadjuvant chemotherapy combined with or without radiotherapy and adjuvant chemotherapy combined with or without radiotherapy after radical resection and those patients with persistent or new occurred recurrence and metastasis. At present, there is no consensus on the second-line treatment strategy for recurrent and metastasis esophageal squamous cell carcinoma after radical resection and there are various clinical options.Therefore, it is of great clinical significance to explore the second-line treatment strategy for these patients.

In recent years, with the development of molecular targeted therapy, it has been applied to the treatment of esophageal cancer, which is not only expected to ensure clinical efficacy, but also to reduce the adverse effects of amount of traditional chemotherapy and radiotherapy.At present, research on targeted therapy for esophageal cancer is gradually increasing. Targeted therapeutic drugs mainly include epidermal growth factor receptor(EGFR) inhibitors,vascular endothelial growth factor(VEGF) inhibitors, monoclonal antibodies, cyclooxygenase(COX) inhibitors and so on.Studies have confirmed that VEGF is highly expressed in the development of various malignant tumors including esophageal cancer, which may be closely related to tumor invasion and metastasis.As a VEGFR tyrosine kinase inhibitor, apatinib mainly treats malignant tumors by inhibiting VEGFR to exert anti-angiogenic effects.Previous studies have confirmed that apatinib was safe and effective in the treatment of advanced gastric cancer and adenocarcinoma of the gastroesophageal junction which was approved by China food and drug administration(CFDA).

In summary, it was difficult to obtain clinical benefits through traditional chemotherapy and radiotherapy for the patients who have recurrence or metastasis tumor even though they have received first-line chemotherapy or combined radiotherapy before, but failed.The aim of this study was to evaluate the safety and efficacy of apatinib, an anti-angiogenesis drug, in the treatment of patients with advanced esophageal squamous cell carcinoma who had recurrence or metastasis after radical resection.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Intervention Model: Single Group Assignment
Intervention Model Description: no special
Masking: None (Open Label)
Masking Description: no special
Primary Purpose: Treatment
Official Title: Prospective,Single-arm,and Exploratory Phase II Clinical Study for the Efficacy of Apatinib in the Treatment of Recurrence or Metastasis of Esophageal Squamous Cell Carcinoma After Radical Resection
Actual Study Start Date : April 2, 2019
Estimated Primary Completion Date : May 30, 2020
Estimated Study Completion Date : May 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: apatinib group
apatinib:500mg po Qd
Drug: apatinib
500mg po Qd




Primary Outcome Measures :
  1. PFS [ Time Frame: 2.5 months ]
    progression-free survival


Secondary Outcome Measures :
  1. OS [ Time Frame: through study completion, an average of 2 year ]
    overall survival

  2. ORR [ Time Frame: through study completion, an average of 2 year ]
    objective remission rate

  3. DCR [ Time Frame: through study completion, an average of 2 year ]
    disease control rate



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age over 18;
  2. ECOG score 0-2;
  3. Postoperative pathology confirmed esophageal squamous cell carcinoma;
  4. Have never received targeted therapy before;
  5. Patients who had failed chemotherapy with platinum or paclitaxel regimens at least once in the past; Note: (1) At least one cycle of drug use, regardless of single or multiple drug combinations;(2) Neoadjuvant concurrent chemoradiotherapy, neoadjuvant chemotherapy or adjuvant chemotherapy are allowed;
  6. According to RECIST version 1.1, there is at least one measurable lesion;
  7. The estimated survival time is more than 3 months;
  8. The main organs are functioning well, and the examination indicators meet the following requirements:

(1) Blood examination: Hemoglobin (>90 g/L) (no blood transfusion within 14 days);The neutrophil count (>1.5×109/L);Platelet count (> 80×109/L); (2)Biochemical examination:Total bilirubin<1.5×upper limit of normal (ULN);alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) are less than 2.5×ULN, ALT or AST are less than 5×ULN if liver metastasis occurred, and creatinine clearance is more than 50 ml/min (Cockcroft-Gault formula); 9.Sign the informed consent; 10.Good compliance, family members agreed to cooperate with survival follow-up;

Exclusion criteria

Subjects may not enter the trial with one of the following:

  1. There were other malignant tumors at the same time, except cured skin basal cell carcinoma and cervical carcinoma in situ of cervix;
  2. Pregnant or lactating women;
  3. Participated in clinical trials of other drugs within one month;
  4. Must be able to swallow tablets;
  5. Any bleeding events with a severe grade of 3 or more in CTCAE 4.0 occurred within 4 weeks before screening;
  6. Patients with central nervous system metastasis or a history of central nervous system metastasis before screening;
  7. Patients with hypertension who can not be well controlled by a single anti-hypertensive drug (systolic pressure > 140 mmHg, diastolic pressure > 90 mmHg); those with a history of unstable angina pectoris; those newly diagnosed as angina pectoris within the first three months of screening or those with myocardial infarction within the first six months of screening; arrhythmia require long-term use of anti-arrhythmic drugs and cardiac insufficiency > Grade II (New York Heart Disease Association Grade) ;
  8. Long-term nonunion of wounds or incomplete healing of fractures;
  9. History of organ transplantation in the past;
  10. Images show that the tumors have invaded important blood vessels or tumor was highly likely to invade important blood vessels during treatment and might cause fatal massive hemorrhage;
  11. Patients who have bleeding tendency with abnormal blood coagulation (PT>16s, APTT>43s, TT>21s, Fbg<2g/L); patients treated with anticoagulant or vitamin K antagonists such as warfarin, heparin or its analogues, use a small dose of warfarin (1 mg orally once daily) or a small dose of aspirin (with a daily dose of no more than 100 mg) for prophylactic purposes under the premise of prothrombin time international normalized ratio (INR)≤1.5;
  12. Arteriovenous thrombosis events occurred in one year ago, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by venous catheterization due to pre-chemotherapy,but healed) and pulmonary embolism;
  13. Patients who have a history of psychotropic drug abuse and were unable to give up or have mental disorders;
  14. Patients who have a history of immunodeficiency or other acquired or congenital immunodeficiency disorders or organ transplantation;
  15. There were concomitant diseases that seriously endanger the safety of patients or affect the completion of the study according to the judgement of the researcher.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03913182


Locations
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China, Shanghai
Shanghai Chest Hospital
Shanghai, Shanghai, China, 200030
Sponsors and Collaborators
Shanghai Chest Hospital
Investigators
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Principal Investigator: Zhigang Li Shanghai Chest Hospital

Publications of Results:
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Responsible Party: Zhiang Li, Director, Head of esophageal surgery, Shanghai Chest Hospital
ClinicalTrials.gov Identifier: NCT03913182     History of Changes
Other Study ID Numbers: SCH0403
First Posted: April 12, 2019    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zhiang Li, Shanghai Chest Hospital:
Esophageal squamous cell carcinoma
apatinib
recurrence
metastasis
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Neoplasm Metastasis
Neoplasms, Second Primary
Esophageal Squamous Cell Carcinoma
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplastic Processes
Pathologic Processes
Disease Attributes
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Apatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action