Patient case: 35-year-old female with Colorectal cancer. Genetic variant: FGFR1 Amplification. Other conditions: None.

Clinical trial: Dose Finding and Pharmacokinetics/Pharmacodynamics Study of Apatinib in the Treatment of Advanced Colorectal Cancer

Summary: RATIONALE:
  Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), and it's anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable.
  PURPOSE:
  1. Studying how well Apatinib works in treating patients.
  2. Finding the efficacy and safety of 500 mg or 750mg Apatinib.
  3. Pharmacokinetics/Pharmacodynamics(PK/PD).
  4. Exploring new outcome measures of antiangiogenic drugs.


Eligibility: 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

Relevance to patient case: not relevant