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

A Randomized, Eploratory, Open Clinical Trial to Compare the Efficacy and Safety of Anlotinib Plus Irinotecan Versus Irinotecan in Patients With Esophageal Squamous Cell Carcinoma

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

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Anlotinib Plus Irinotecan; Drug: Irinotecan

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Feng Wang, doctor; Phone Number: 860013938244776; Email: fengw010@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Qingxia Fan, doctor

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:

• 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 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: 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	Drug: Anlotinib Plus Irinotecan; Anlotinib QD po.and Irinotecan Day 1,8 ivgtt.
Active Comparator: Irinotecan; Irinotecan Day 1,8 ivgtt and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent	Drug: Irinotecan; Irinotecan Day 1,8 ivgtt

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress free survival (PFS)	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.	up to 24 months
Disease Control Rate (DCR)	The proportion of patients with a best overall response of confirmed complete or partial response, or stable disease (CR + PR + SD)	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	The time from treatment initiation until death from any reason	up to 24 months
Objective Response Rate (ORR)	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	up to 24 months
Quality of life score	Each 42 days up to intolerance the toxicity or PD	up to 24 months
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Until initiation of new anticancer treatment	up to 24 months
NGS(Next Generation Sequencing) detecting	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	up to 12 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 23, 2017
• First Submitted That Met QC Criteria: December 23, 2017
• First Posted (Actual): January 2, 2018

Study Record Updates

• Last Update Posted (Actual): September 2, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Anlotinib
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: ALTN-11-II-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No