Apatinib in the Treatment of Recurrence or Metastasis of Esophageal Cancer

February 3, 2020 updated by: Zhigang Li, Shanghai Chest Hospital

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

39

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • Recruiting
        • Shanghai Chest Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Xufeng Guo, doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: apatinib group
apatinib：500mg po Qd
Drug: apatinib
500mg po Qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: 2.5 months
progression-free survival
2.5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: through study completion, an average of 2 year
overall survival
through study completion, an average of 2 year
ORR
Time Frame: through study completion, an average of 2 year
objective remission rate
through study completion, an average of 2 year
DCR
Time Frame: through study completion, an average of 2 year
disease control rate
through study completion, an average of 2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Chest Hospital

Investigators

  • Principal Investigator: Zhigang Li, Shanghai Chest Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 2, 2019

Primary Completion (Anticipated)

May 30, 2020

Study Completion (Anticipated)

May 30, 2021

Study Registration Dates

First Submitted

April 10, 2019

First Submitted That Met QC Criteria

April 10, 2019

First Posted (Actual)

April 12, 2019

Study Record Updates

Last Update Posted (Actual)

February 5, 2020

Last Update Submitted That Met QC Criteria

February 3, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCH0403

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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