Apatinib and Irinotecan Combination Treatment in Unresectable or Metastatic Esophageal Squamous Cell Carcinoma

Apatinib and Irinotecan Combination Treatment in Unresectable or Metastatic Esophageal Squamous Cell Carcinoma Patients Failed in First-line Chemotherapy: A Phase II Study

Esophageal cancer is a common malignant disease worldwide especially in china. Though esophagectomy and definitive chemoradiotherapy are standard treatments, disease relapses in many patients and the prognosis of metastatic ESCC is still poor. For patients with unresectable or metastatic ESCC, chemotherapy is an important treatment alone or with radiotherapy. Taxane, platinum, and fluoropyrimidine have been reported effective in ESCC and is used as first-line treatment of ESCC. As for 2nd-line treatment, both irinotecan and taxane had been recommended based on data from clinical trials which were most enrolled esophageal or esophageal-gastric junction adenocarcinoma and with only small sample size. Therefore, it is still urgently needed to explore effective 2nd-line treatment for ESCC.

Apatinib, also known as YN968D1, is an orally antiangiogenic agents. Preclinical and clinical data had shown that it is effective in the treatment of a variety of solid tumors including esophageal cancer. It had been approved as a 3rd-line treatment for patients with advanced gastric cancer by state FDA of China in 2014. And the safety data showed that hemorrhage is rare and non-fetal which is different from bevacizumab.

Therefore, the investigators initialize this phase II study to explore the efficacy and safety of irinotecan and apatinib combination treatment in unresectable or metastatic ESCC patients who failed in 1st-line chemotherapy or chemoradiotherapy.

Study Overview

• Status: Suspended
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Irinotecan; Drug: Apatinib

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital / Peking University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 70 years. Both genders are eligible.
• Patients must have histologically confirmed esophageal squamous cell carcinoma with unresectable or metastatic disease.
• With measurable or evaluable disease defined by RECIST 1.1 criteria by multi-slice spiral CT or MR scan.
• Failed in or disease progressed after fist-line chemotherapy (A. If failed in preoperative chemotherapy / chemoradiotherapy or disease progressed in 24 weeks after esophagectomy, the preoperative chemotherapy/ chemoradiotherapy is regard as first-line chemotherapy. B. If failed in definitive chemoradiotherapy or disease progressed in 24 weeks after definitive chemoradiotherapy, the definitive chemoradiotherapy is regard as first-line chemotherapy; C. If failed in or relapse in 24 weeks after adjuvant chemotherapy, the adjuvant chemotherapy is regard as first line chemotherapy).
• Patients must have a performance status of 0-2 on the ECOG scale.
• Life expectancy ≥3 months.
• With normal marrow, liver and renal function:a hemoglobin (HGB) of ≥110g/L (without blood transfusion during 14 days); a neutrophil count of ≥2.0×109/L; a platelet count of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL) or ≤3 UNL in case of liver metastasis. a creatinine (Cr) of ≤ 1.5 UNL or a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis. Fecal occult blood (-); Urine test: protein<(++) or <1.0g per 24 hours.
• Without bleeding and thrombosis disease.
• With normal coagulation function: APTT, PT and INR, each ≤ 1.5 ULN
• With normal electrocardiogram results and no history of congestive heart failure.
• Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug.
• With good compliance and agree to accept follow-up of disease progression and adverse events.
• With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.

Exclusion Criteria:

• Patients who have received irinotecan or apatinib in previous treatment.
• Other pathological type cancers of esophagus except for squamous cell carcinoma
• Uncontrolled hypertension (Treatment of antihypertensive drugs cannot reduced to the normal range: systolic pressure ≤140 mmHg and diastolic pressure ≤90 mmHg)
• With ≥grade 2 coronary heart disease, arrhythmia (including QTc interval prolongation male >450 ms, women >470 ms)
• Cannot take oral tables including uncontrolled vomiting, chronic diarrhea and intestinal obstruction.
• With potential bleeding risk of GI including (1) peptic ulcer and fecal occult blood (++ - +++); (2) melena or hematemesis history in last 3 months;(3) In case of fecal occult blood (+) or (+/-),fecal occult blood examination must be repeat in one week. If fecal occult blood is still (+) or (+/-),endoscopy is required and if there are ulcer or other diseases with bleeding risk in the opinion of the investigators. (4) Primary tumour lesion is of deep ulcer and in the opinion of the investigators may place the patient at risk of fetal bleeding or GI perforation.
• Urine test: protein>(++) or >1.0g per 24 hours.
• With abnormal coagulation function (INR>1.5 ULN, APTT>1.5 ULN),
• With thrombosis or receiving anticoagulant treatment.
• With serious diseases such as congestive heart failure, uncontrolled myocardial infarction and arrhythmia, liver failure and renal failure.
• With brain metastasis
• Pregnant or lactated women.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination treatment; Combination treatment of irinotecan and apatinib.	Drug: Irinotecan; Irinotecan 150mg/m2, repeated very 2 weeks for 3 to 6 cycles.; Other Names: CPT-11; Drug: Apatinib; Apatinib 500 mg oral take, daily; Other Names: YN968D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	The percentage of patients with CR, PR, and SD response after 3 cycles' treatment according to RESIST v1.1 criteria.	From enrollment to 3 months after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: All reported adverse events (NCI CTCAE 4.0 criteria)	All reported adverse events (NCI CTCAE 4.0 criteria) during treatment and one months after treatment.	From enrollment to progression of disease or 1 months after treatment.
Objective response rate	Clinical response rate of treatment (CR+PR) according to RESIST v1.1 criteria	From enrollment to 3 months after treatment
Median progression-free survival time	The length of time from enrollment until the time of progression of disease	From enrollment to progression of disease. Estimated time is about 4 months
Median overall survival time	The length of time from enrollment until the time of death.	From enrollment to death of patients, estimated about 8 months.

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Jun Jia, M.D., Beijing Cancer Hospital/ Peking University Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2017
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 14, 2017
• First Submitted That Met QC Criteria: August 15, 2017
• First Posted (Actual): August 16, 2017

Study Record Updates

• Last Update Posted (Actual): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 16, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Apatinib; Irinotecan
• 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; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Apatinib
• Other Study ID Numbers: AHEAD-HBE002

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