Clinical trial NCT02649361: Study of Anlotinib in Patients With Esophageal Squamous Cell Carcinoma (ALTER1102)
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Trial to Compare the Efficacy and Safety of Anlotinib Versus Placebo in Patients With Esophageal Squamous Cell Carcinoma(ALTER1102)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Anlotinib
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-01-07
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the effects and safety of Anlotinib with placebo in patients with esophageal squamous cell carcinoma(ESCC).


Eligibility criteria: Inclusion Criteria:

* Histological documentation of esophageal squamous cell carcinoma；
* Advanced esophageal squamous cell carcinoma with distant metastasis(Stage IV),at least one measurable lesion (by RECIST1.1)
* Patients who at least have failed to a platinum-based chemotherapy treatment or chemotherapy containing paclitaxel.

Note: (1) Each line treatment refers to treatment duration at least one cycle using monotherapy or drug combination; (2)Adjuvant chemotherapy or neoadjuvant chemoradiation is permitted before the study (if disease recurred during adjuvant chemotherapy/neoadjuvant chemoradiation or recurred within 6 months after stopping treatment, adjuvant chemotherapy/neoadjuvant chemoradiation can be considered as first line systemic chemotherapy;

* 18-75 years,ECOG PS:0-2,Life expectancy of more than 3 months
* 4 weeks or more from the last cytotoxic therapy, radiation therapy or surgery
* Main organs function is normal
* Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped
* Patients should participate in the study voluntarily and sign informed consent

Exclusion Criteria:

* Patients whose primary lesion with active bleeding within 2 months
* Primary lesion not resected and has not shrinked after radiation therapy
* Patients who have been failure with anti-tumor angiogenesis drug treatment
* Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.)
* Brain metastases patients with symptoms or symptoms controlled \< 3 months
* Patients with any severe and/or unable to control diseases，including：

  1. Blood pressure unable to be controlled ideally(systolic pressure≥150 mmHg，diastolic pressure≥100 mmHg);
  2. Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including QT≥480ms) and patients with Grade 1 or higher congestive heart failure (NYHA Classification);
  3. Patients with active or unable to control serious infections;
  4. Patients with cirrhosis, decompensated liver disease, or active hepatitis;
  5. Patients with poorly controlled diabetes (fasting blood glucose(FBG)\>10mmol/L)
  6. Urine protein ≥ ++，and 24-hour urinary protein excretion\>1.0 g confirmed
* Patients with non-healing wounds or fractures
* Patients with any CTC AE Grade 1 or higher bleeding events occurred in the lungs or any CTC AE Grade 2 or higher bleeding events occurred within 4 weeks prior to assignment;Patients with any physical signs of bleeding diathesis or receiving thrombolysis and anticoagulation
* Patients with arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism
* Patients with drug abuse history and unable to get rid of or Patients with mental disorders
* Imaging showed tumors have involved important blood vessels or by investigators determine likely during the follow-up study and cause fatal hemorrhage
* Patients participated in other anticancer drug clinical trials within 4 weeks
* History of immunodeficiency
* Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment

Primary outcomes:
measure: Progress free survival (PFS)
timeFrame: From randomization，each 42 days up to PD or death(up to 24 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to 24 months)
measure: Objective Response Rate (ORR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Harbin
country: China
facility: Harbin medical university affiliated tumor hospital
state: Heilongjiang
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical College
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Xian
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Hospital
state: Tianjin
city: Wulumuqi
country: China
facility: Cancer Hospital of Xinjiang Medical University
state: Xinjiang
Study officials:
References:
citation: Huang J, Xiao J, Fang W, Lu P, Fan Q, Shu Y, Feng J, Zhang S, Ba Y, Zhao Y, Liu Y, Bai C, Bai Y, Tang Y, Song Y, He J. Anlotinib for previously treated advanced or metastatic esophageal squamous cell carcinoma: A double-blind randomized phase 2 trial. Cancer Med. 2021 Mar;10(5):1681-1689. doi: 10.1002/cam4.3771. Epub 2021 Feb 14.