Clinical trial NCT03210064: Clinical Study of Apatinib and 5-Fu Combination Regimen to Treat Advanced Colorectal Cancer Patients
Official title: A Phase II Clinical Trial Study on Apatinib and 5-Fu Combination Regimen in the Treatment of Advanced Colorectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Apatinib
Lead sponsor: Hubei Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2017-07-06
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental: apatinib combined with 5-Fu
Primary purpose: TREATMENT

Brief summary: This study makes an observation over the objective response rate of Apatinib and 5-Fu combination regimen in the three-line treatment of metastatic colorectal cancer. All the participants will randomly receive the treatment of Apatinib and 5-Fu combination regimen or 5-Fu.

Detailed description: 5-Fu chemotherapy is an effective therapy for colorectal cancer. Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), with a decrease in VEGF-mediated endothelial cell migration, proliferation, and tumor microvascular density. A phase II trail of Apatinib has been demonstrated that Apatinib is safe to treat the metastatic colorectal cancer and the disease control rate can reach 50%.

Eligibility criteria: Inclusion Criteria:

* 18 and ≤ 70 years of age

  * Histological confirmed advanced or metastatic colorectal Cancer，at least one measurable lesion, larger than 10 mm in diameter by spiral CT scan(scanning layer ≤ 5 mm )
  * Have failed for ≥ 2 lines of chemotherapy
  * Life expectancy of more than 3 months
  * ECOG performance scale ≤ 1
  * Duration from the last therapy is more than 6 weeks for nitroso or mitomycin More than 4 weeks for operation, radiotherapy or cytotoxic agents
  * Adequate hepatic, renal, heart, and hematologic functions (platelets \> 80 × 10E+9/L, neutrophil \> 1.5 × 10E+9/L, serum creatinine ≤ 1×upper limit of normal(ULN), bilirubin \< 1.25 ULN, and serum transaminase ≤ 2.5× ULN)
  * Child bearing potential, a negative urine or serum pregnancy test result before initiating apatinib, must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article.
  * Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

* History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
* Pregnant or lactating women
* Preexisting uncontrolled hypertension defined as more than 140/90 mmHg despite using single medical therapy, more than class I (NCI CTCAE 3.0 ) myocardial ischemia, arrhythmia(including QTcF:male ≥ 450 ms, female ≥ 470 ms), or cardiac insufficiency myocardial ischemia, arrhythmia, or cardiac insufficiency
* Before or at the same time any, second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
* Any factors that influence the usage of oral administration Evidence of CNS metastasis
* URT: urine protein ≥ (++)and \> 1.0 g of 24 h
* PT, APTT, TT, Fbg abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation
* Abuse of drugs
* Certain possibility of gastric or intestine hemorrhage
* Less than 4 weeks from the last clinical trial
* Viral hepatitis type B or type C
* Prior VEGFR inhibitor treatment
* Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study

Primary outcomes:
measure: ORR
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.
Secondary outcomes:
measure: DCR
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.
measure: PFS
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.
measure: OS
timeFrame: From assignment of the first subject until 30 death events observed, up to 2 years.
measure: QoL
timeFrame: From assignment of the first subject to 3 months later after the last participant is recruited.
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Hui ting Xu
state: Hubei
Study officials:
affiliation: Hu bei CH
name: Yan li Nie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hu bei CH
name: Liu Yang, MD
role: STUDY_DIRECTOR
References:
citation: Chen R, Yang L, Hu S, Yin Z, Nie Y, Xu H, Zhong Y, Zhu Y, Liang X, Xu H. Apatinib plus 5-fluorouracil as a third or subsequent-line treatment option for metastatic colorectal cancer: a phase-II, single-arm, prospective study. Ann Transl Med. 2022 Jan;10(2):100. doi: 10.21037/atm-22-77.