Clinical trial NCT03190616: Apatinib in Refractory Colorectal Cancer
Official title: A Single Arm, Open Label, Multicenter Exploratory Study of Apatinib in Patients With Metastatic Colorectal Cancer (CRC) Who Have Progressed After Standard Second Line Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
name: Beijing gene plus technology co., LTD
First posted: 2017-06-19
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Limited agents have been approved after standard first and second line treatment. Regorafenib and Trifluridine/Tipiracil (TAS-102) are still not approved in China.Apatinib has shown significant efficacy in refractory advanced gastric cancer regarding PFS and OS with controllable toxicity.This study is aimed to explore the efficacy,safety as well as predictive biomarker in advanced colorectal cancer failed to standard therapy in Chinese population.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
* Subjects with metastatic colorectal cancer(CRC) (Stage IV).
* Subjects must have failed at least two lines of prior treatment, which must include a fluoropyrimidine, oxaliplatin and irinotecan.
* Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy.
* Subjects who have withdrawn from standard treatment due to unacceptable toxicity and precluding retreatment with the same agent prior to progression of disease will also be allowed.
* Prior treatment with bevacizumab and/or cetuximab will be allowed.
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
* Life expectancy of at least 3 months.
* Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol.
* assigned informed consent.

Exclusion Criteria:

* Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
* Participants of other clinical trial within 4 weeks.
* Diseases which will impact the absorption of apatinib, eg. dysphagia, chronic diarrhea, bowl obstruction
* Hemorrhage events of ≥grade 3 within 4 weeks.
* known central nervous system metastasis.
* Uncontrolled hypertension. (Systolic blood pressure 140 mmHg or diastolic pressure 90 mmHg despite optimal medical management). Unstable angina,congestive heart failure,Myocardial infarction, Cardiac arrhythmias requiring anti-arrhythmic therapy.
* urine protein ≥++ and 24h urine protein more than 1.0g.
* Chronically green wound or bone fracture.
* Arterial or venous thrombotic or embolic events.
* Tumor invading important blood vessel with high risk of severe hemorrhage.
* Abnormal coagulation function.
* thromboemboli events within 6 months.

Primary outcomes:
measure: Progression-free Survival(PFS)
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From assignment of the first subject until 40 death events observed, up to 2 years.
measure: Disease control rate (DCR)
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019
measure: Objective response rate(ORR)
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019
measure: Quality of life
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019
measure: relationship between the tumor molecular burden & gene mutation and the drug efficacy.
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.The last participant will be recruited before Mar 30,2019.
Other outcomes:
Locations:
city: Changzhou
country: China
facility: the second hospital of Changzhou city
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing 81 Hospital
state: Jiangsu
city: Nanjing
country: China
facility: the first affiliated hospital with Nanjing Medical University
state: Jiangsu
city: Wuxi
country: China
facility: Jiangnan University affiliated hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Yanhong Gu, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16.
citation: Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.