Study of Anlotinib Plus Irinotecan in Patients With Esophageal Squamous Cell Carcinoma

Phase 2

• Conditions: Esophageal Squamous Cell Carcinoma
• Interventions: Drug: Anlotinib Plus Irinotecan; Drug: Irinotecan

• Registration Number: NCT03387904
• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University

Brief Summary

To compare the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with esophageal squamous cell carcinoma(ESCC).

Detailed Description

In recent years, anti-angiogenic therapy has made some progress in the treatment of advanced esophageal squamous cell carcinoma.In clinical use, the efficacy of antiangiogenic monotherapy was low, with a median progression-free survival (PFS) of only 3 to 4 months.We conducted a randomized, open clinical Trial to evaluate efficacy and safety of anlotinib hydrochloride combined with irinotecan versus irinotecan monotherapy in patients with advanced esophageal squamous cell carcinoma.

Study Timeline

• Study First Submitted: 2017-12-23
• Study First Submitted QC: 2017-12-23
• Study First Posted: 2018-01-02
• Study Start: 2019-01-13
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-30
• Last Update Posted: 2021-09-02
• Primary Completion: 2021-12-01
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Histological documentation of esophageal squamous cell carcinoma;
• At least one measurable lesion (by RECIST1.1);
• Patients who have failed to a chemoradiation treatment;
• 18-75，ECOG PS:0-1,Life expectancy of more than 12 weeks;
• No treated with molecular targeted drugs;
• Main organs function is normal;
• Patients should participate in the study voluntarily and sign informed consent;

Exclusion Criteria

• Allergic to anlotinib and/or its excipients;

• Patients with any severe and/or unable to control diseases，including：

  1. Blood pressure unable to be controlled ideally(systolic pressure >140 mmHg，diastolic pressure>90 mmHg);
  2. Patients with Grade 2 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including QT≥450ms for male， QT≥470ms for female) and patients with Grade 3 or higher congestive heart failure (NYHA Classification) or LVEF<50%;

• Patients with a clear Gastrointestinal bleeding tendency include the following situations: Local active ulcer lesions, and fecal occult blood (+ +) ; The patient had a history of black and hematemesis within 2 months;

• Patients with a bleeding tendency and INR>1.5,APTT>1.5 ULN ;

• Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.);

• Patients with active brain metastasis, cancerous meningitis, spinal cord compression patients or found in Screening stage;

• Patients treated with VEGFR inhibitor;

• Patients with drug abuse history and unable to get rid of or Patients with mental disorders;

• Patients participated in other anticancer drug clinical trials within 4 weeks;

• Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anlotinib Plus Irinotecan	Anlotinib Plus Irinotecan	Anlotinib QD po.and Irinotecan Day 1,8 ivgtt. Both should be continued until disease progression or intolerable toxicity or patients withdrawal of consent
Irinotecan	Irinotecan	Irinotecan Day 1,8 ivgtt and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent

Primary Outcome Measures

Name	Time	Method
Progress free survival (PFS)	up to 24 months	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm.
Disease Control Rate (DCR)	up to 24 months	The proportion of patients with a best overall response of confirmed complete or partial response, or stable disease (CR; + PR + SD)

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	up to 24 months	The time from treatment initiation until death from any reason
Objective Response Rate (ORR)	up to 24 months	The proportion of patients with a confirmed complete response or partial response on two consecutive occasions≥4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Quality of life score	up to 24 months	Each 42 days up to intolerance the toxicity or PD
NGS(Next Generation Sequencing) detecting	up to 12 months	The sample for NGS detecting can be gotten form storage tumor tissue specimens. It must be better collecting the new tumor tissue specimens after tumor progress
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	up to 24 months	Until initiation of new anticancer treatment

Trial Locations

Locations (1)

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China