A Study of Second-line Treatment of Postoperative Recurrence and Metastasis of Esophageal Cancer Treated With Apatinib

Randomized, Open, Positive Drug Control, Multicenter Clinical Study of Second-line Treatment of Postoperative Recurrence and Metastasis of Esophageal Squamous Cell Carcinoma With Chemotherapy in Patients Treated With Apatinib Mesylate

A study of second-line treatment of postoperative recurrence and metastasis of esophageal squamous cell carcinoma after chemotherapy with apatinib mesylate

Study Overview

• Status: Withdrawn
• Conditions: Esophageal Neoplasms
• Intervention / Treatment: Drug: Apatinib; Drug: The chemotherapeutic drug chosen by the investigator.

Detailed Description

This is a randomized, open-label, multi-center, phase II clinical trial initiated by a investigator to observe and evaluate the efficacy of apatinib in the treatment of patients with failed first-line treatment after recurrence and metastasis of esophageal squamous cell carcinoma. Effectiveness and security.

• Study Type: Interventional
• Phase: Phase 2

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:

• Pathological/histological diagnosis of esophageal squamous cell carcinoma; and at least one measurable lesion according to RECIST criteria (version 1.1);
• Patients who have undergone radical resection of esophageal cancer and who have failed after first-line systemic chemotherapy (which may include platinum, taxane or fluorouracil) after recurrence (recurrence of postoperative adjuvant chemotherapy within 6 months) Considered as first-line treatment, and the same progress in the field of radiation can be seen as recurrence;
• Age: 18-75 years old; both men and women;
• ECOG PS Rating: 0-1 points;
• Estimated survival period ≥ 3 months;
• ≥ 4 weeks from the last cytotoxic drug;

• The main organs function normally, that is, meet the following criteria:

  • Blood routine examination:

    • HB≥90 g/L; (no blood transfusion within 14 days)
    • ANC ≥ 1.5 × 109 / L;
    • PLT ≥ 80 × 109 / L;

  • Biochemical examinations must meet the following criteria:

    • ALT and AST < 2.5 ULN; if there is liver metastasis, ALT and AST < 5 ULN;
    • TBIL ≤ 1.5ULN;
    • Plasma Cr≤1.5ULN or creatinine clearance (CCr)≥60ml/min
• Subjects volunteered to participate in the study, signed informed consent, and were well-adhered to follow-up.
• Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months of the end of the study; negative serum or urine pregnancy tests within seven days prior to study enrollment And must be non-lactating patients; males should agree to patients who must use contraception during the study period and within 6 months after the end of the study period.

Exclusion Criteria:

• Those who have used anti-tumor angiogenesis drugs to treat failure;
• Patients with residual esophagus, residual stomach or anastomotic recurrence;
• Unable to swallow, chronic diarrhea and intestinal obstruction, which obviously affect the taking and absorption of drugs;
• Patients with brain metastases with symptoms or symptoms controlled for less than 3 months;
• Long-term unhealed wounds and fractures;
• Have clear gastrointestinal bleeding concerns (such as local active ulcer lesions, fecal occult blood above ++), history of gastrointestinal bleeding within 6 months; coagulation abnormalities (PT>16 s, APTT>43 s, TT>21 s, Fbg< 2 g/L), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
• Overactive/venous thrombosis occurred within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism;
• Imaging shows that the tumor has invaded the important perivascular circumference or that the patient is likely to invade the important blood vessels during the follow-up study and cause fatal bleeding.
• Persons with a history of psychotropic substance abuse who are unable to resolve or have a mental disorder;
• Participated in other clinical trials of anti-tumor drugs within four weeks;
• Have a history of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
• According to the investigator's judgment, there are serious concomitant illnesses that compromise the safety of the patient or affect the patient's completion of the study.

• Patients with any severe and/or uncontrolled diseases, including:

  • Blood pressure control is unreasonable (retraction pressure >150mmHg, diastolic pressure >100mmHg) Patients: I have myocardial ischemia or myocardial infarction above grade I, arrhythmia (including QT interval >440ms) and grade I cardiac insufficiency;
  • Active or uncontrolled serious infections;
  • Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;
  • Poor diabetes control (fasting blood glucose FBG>10mmol/L);
  • Urine routine indicates urinary protein >++, and confirmed 24-hour urine protein quantitation >1.0g.
• The investigator believes that it is not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group; It is recommended that the initial dose of apatinib is 500mg po qd. Adjust the dose to 750mg po qd or maintain the original dose according to the patient's medication response for about 2 weeks. If there is grade III or above, or grade II and above non-hematologic toxicity, allow the dose to be lowered 2 times.	Drug: Apatinib; It is recommended that the initial dose of apatinib is 500mg po qd. Adjust the dose to 750mg po qd or maintain the original dose according to the patient's medication response for about 2 weeks. If there is grade III or above, or grade II and above non-hematologic toxicity, allow the dose to be lowered 2 times.
Active Comparator: Control group; The chemotherapeutic drug chosen by the investigator (if not used in the previous treatment regimen, it cannot be selected). The choice of chemotherapy regimen is based on the medication habits of the drug delivery doctor and the specific circumstances of the patient. In addition, the following regimens may be selected as monotherapy or combination: docetaxel 60-75 mg/m2d1 q3w; irinotecan 150-180 mg/m2 d1 q2w until disease progression or patient decease. If the adverse event grade 3 and above Or non-hematologic toxicity of grade II and above appeared, allowing the dose to be lowered twice.	Drug: The chemotherapeutic drug chosen by the investigator.; The choice of chemotherapy regimen is based on the medication habits of the drug delivery doctor and the specific circumstances of the patient. In addition, the following regimens may be selected as monotherapy or combination: docetaxel 60-75 mg/m2d1 q3w; irinotecan 150-180 mg/m2 d1 q2w until disease progression or patient death. If grade 3 and above or non-hematologic toxicity of grade II and above adverse event appeared, allowing the dose to be lowered twice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	progression-free survival	One year from admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	One year from admission
DCR	disease control rate	One year from admission
ORR	Objective Response Rate	One year from admission

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Recurrence; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: Nanjing Drum Tower Hospital

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No