Safety and Efficacy Study of Famitinib in Patients With Advanced Colorectal Adenocarcinoma（FACT）

Colorectal Cancer Metastatic Clinical Trial

— FACT  

Official title:

A Multicenter，Randomized, Double-blind, Placebo-controlled Trial of Famitinib in Patients With Advanced Colorectal Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02390947
• Other study ID #: HR-FMTN-CRC-FACT
• Status: Completed
• Phase: Phase 3
• Start date: January 2015
• Est. completion date: July 2019

Study information

• Verified date: May 2017
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Famitinib is a tyrosin-inhibitor agent targeting at c-Kit, VEGFR2, PDGFR, VEGFR3, Flt1 and Flt3, whose anti-tumor and anti-angiogenesis effects have been validated in preclinical tests. In PhaseⅡb study, a significantly improved Progression Free Survival (PFS) was found in patients with advanced colorectal cancer treated with Famitinib compared to placebo. On the other hand, the toxicity of Famitinib was manageable in both PhaseⅠand Ⅱb studies.

The purpose of this study is to determine whether Famitinib can improve Overall Survival (OS) compared with placebo in total 540 patients with advanced colorectal cancer who have failed in previously received at least two lines of standard chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 543
• Est. completion date: July 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female patients aged 18 to 75 (including 18 and 75) at the time of Informed Consent

2. Pathologically confirmed advanced colorectal adenocarcinoma (all the other histological types are excluded)

3. Treatment failure in previously received standard therapy (at least two lines), which must include 5-Fu, irinotecan and oxaliplatin

Definition of "treatment failure":

A.Disease progression during experimental drug treatment or within 3 months after the last treatment, with definite imaging or clinical evidences;

B.For patients abandoning chemotherapy because of intolerance of advent events, hematologic toxicity is required to reach =Grade IV (platelet decrease = Grade III ), and nonhematologic toxicity is required to reach =Grade III , according to NCI CTCAE 4.0. Furthermore, the original treatment should be not tolerated any more when it is repeated to the same patient, judged by investigators.

Note:

A.When adjuvant therapy including oxaliplatin was previously used, at least 9 courses of FOLFOX (2 weeks regimens), 6 courses of CapeOX (3 week regimen), or 750mg/m^2 cumulative consumption of oxaliplatin, are required. Adjuvant therapy will be regarded as the first-line treatment when disease progressed during or within 6 months after treatments

B.Monoclonal antibody drugs (bevacizumab, cetuximab, panitumumab, aflibercept, etc.) are allowed to combine with prior chemotherapy.

4. At least one measurable targeting lesion according to RECIST 1.1 (The diameter of tumor and lymph node lesion should be = 10 mm and 15mm, respectively, with scanning layer = 5 mm and without local treatment)

5. Eastern Cooperative Oncology Group (ECOG) performance status:0-1.

6. Life expectancy = 3 months

7. Adequate function of major organs, meaning the following criteria should be met within 14 days before randomization:

A.Routine blood test:

1. Hemoglobin > 90g/L (not received blood transfusion or drugs to incraese RBC, Hb, WBC and PLT in 14 days before screening )

2. Neutrophils > 1.5×10^9/L

3. Platelets > 100×10^9/L

B. Blood biochemistry:

4. Total bilirubin < 1.25×the upper limit of normal (ULN)

5. Serum transaminase = 2×ULN (= 5×ULN, If existing liver metastases)

6. Creatinine clearance rate = 60ml/min (Cockcroft-Gault Formula)

C.Doppler echocardiography assessment: Left ventricular ejection fraction (LVEF) = 50%

8. Having recovered from impairments of other therapy before taking research drugs (more than 6 weeks from the last treatment of Nitroso or MMC, more than 4 weeks from the last treatment of other cytotoxic drugs, targeted drugs, radiotherapy or operation, with completely healed wound, more than 2 weeks from the last treatment of Chinese traditional and patent medicine)

9. Signed and dated informed consent

10. Good compliance of patients and agreement of their family members to cooperate on the follow-up of survival.

Exclusion Criteria:

1. Second malignancies, except for cured skin basal cell carcinoma and carcinoma in-situ of uterine cervix, before or during screening

2. Previously received therapy of tyrosine kinase inhibitor agent targeting at VEGFR, e.g. famitinib, sorafenib, sunitinib, regorafenib

3. Having joined in other clinical trials within 4 weeks

4. Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.)

5. Having haemorrhage history, = Grade ? (NCI CTCAE 4.0 ) haemorrhage occurred within 4 weeks before screening

6. Known central nervous system (CNS) metastasis or having CNS metastasis history before screening. CT or MRI scan should be received 28 days before randomization when CNS metastases is clinically suspected

7. Uncontrolled hypertension with single medical therapy (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg), History of unstable angina pectoris or newly diagnosed unstable angina pectoris within 3 months before screening, myocardial infarction events within 6 months before screening, Arrhythmias (QTcF: =450ms in male, = 470ms in female) needed long-term treatment of drugs, = class II cardiac insufficiency by New York Heart Association (NYHA) classification

8. urinary protein = ++ or 24-hour urinary protein = 1.0 g

9. Chronic untreated wounds or fractures

10. Tumor invasion around major vessels shown by imaging, high risk of major vascular invasion leading to massive hemorrhage judged by investigators

11. Abnormal international normalized ratio (INR) of patients with coagulation dysfunction and hemorrhagic tendency at 14 days before randomization. Application of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues. However, low doses of warfarin (1mg orally, once daily) or aspirin (between 80mg to 100mg daily) can be used for prevention on the premise of INR = 1.5

12. Artery/venous thromboembolic events occurred within 1 year before screening, such as cerebral vascular accident (including transient ischemic attack), deep vein thrombosis (except for recovered venous thrombosis judged by investigators, which was caused by venous catheter in previous chemotherapy) and pulmonary embolism, etc.

13. All female patients who are not surgically sterilized or postmenopausal refusing to take a reliable method of birth control during the study and within 6 months after the last dose of test article. All female patients in breastfeeding period or in child-bearing period with a positive urine or serum pregnancy test result before randomization. All male subjects who are not surgically sterilized refusing to take a reliable method of birth control during the study and within 6 months after the last dose of test article.

14. Preexisted thyroid dysfunction, thyroid function cannot be controlled within normal range even using medical therapy

15. History of psychiatric drug abuse and addiction, dysphrenia

16. Symptomatic pleural effusion, hydropericardium or ascites needed clinical intervention or being stable less than 4 weeks.

17. History of Immunodeficiency, acquired or congenital immunodeficiency, history of organ transplantation

18. Known active HBV or HCV infection companion with hepatic dysfunction

19. Concomitant disease judged by investigators that may bring serious harm to the safety of patients or the completion of this study

Related Conditions & MeSH terms

• Adenocarcinoma
• Colorectal Cancer Metastatic
• Colorectal Cancer Recurrent
• Colorectal Neoplasms

Intervention

Drug:
• Famitinib
25 mg p.o. qd
• Placebo
25 mg p.o. qd

Locations

Country	Name	City	State
China	Beijing Cancer Hospital, Peking University	Beijing	Beijing
China	Beijing Chao-yang Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Chinese Academy of Medical Sciences Cancer Hospital	Beijing	Beijing
China	PLA Hospital 301	Beijing	Beijing
China	Cancer Hospital of Jilin province	Changchun	Jilin
China	The First Affiliated Hospital of Jilin University	Changchun	Jilin
China	Cancer Hospital of Hunan Province	Changsha	Hunan
China	The Third Xiangya Hospital of Cental South University	Changsha	Hunan
China	The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	The Third Affiliated Hospital of The Third Military Medical University	Chongqing	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Cancer center, Sun Yet-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University of Chinese Medicine	Guangzhou	Guangdong
China	Hainan General Hospital	Hainan	Hainan
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Cancer Hospital of Yunnan Province	Kunming	Yunnan
China	Cancer Hospital of Jiangxi Province	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Cancer Hospital of Jiangsu Province	Nanjing	Jiangsu
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Cancer Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	Fudan University Cancer Hospital	Shanghai	Shanghai
China	Ruijin Hospital, Shanghai jiaotong University, School of Medicine	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Zhongshan Hospital of Fudan University	Shanghai	Shanghai
China	Cancer Hospital of Liaoning Province	Shenyang	Liaoning
China	Chinese Medical University First Hospital	Shenyang	Liaoning
China	Cancer Hospital of Tianjin City	Tianjin	Tianjin
China	People's Hospital of Tianjin City	Tianjin	Tianjin
China	Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Wuhan General Hospital of Guangzhou Military	Wuhan	Hubei
China	Cancer Hospital of Shanxi Province	Xian	Shanxi
China	Tangdu Hospital of The Fouth Military Medical University	Xian	Shanxi
China	The first affiliated hospital of Xinxiang medical university	Xinxiang	Henan
China	The Affiliated Hospital of Xuzhou Medical Collage	Xuzhou	Jiangsu
China	Cancer Hospital of Henan Province	Zhengzhou	Henan
China	The First affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival(OS)		3 years
Secondary	Progression Free Survival(PFS)		1.5 years
Secondary	Objective response rate(ORR)		6 months
Secondary	Disease Control Rate(DCR)		1.5 years
Secondary	Quality of Life as measured by EORTC QLQ-C30(3.0)		1.5 years
Secondary	The incidence of Adverse Events		3 years
Secondary	The severity of Adverse Events		3 years