| Eligibility |
Inclusion Criteria:
1. Patients with recurrent resistant GTN previously received twice or more combination
chemotherapy before enrolment;
2. In the 20000 FIGO staging and classification, a risk score of 7 and above 7
(Considered high risk) or resistant recurrent placental site trophoblastic tumor or
resistant recurrent epithelial trophoblastic tumor;
3. Aged 18-70 years;
4. An Eastern Cooperative Oncology Group performance status of 0-2;
5. abnormal serum HCG level;
6. Expected survival = 4 months;
7. The function of vital organs meets the following requirements: Hemoglobin=80g/L;
Absolute neutrophil count=1.5*109/L;Platelets=100
*109/L; Creatinine=1.5 times ULN; Urea nitrogen=2.5 times ULN; Total Bilirubin=ULN;
ALT and AST = 2.5 times ULN; Albumin=25g/L; TSH=ULN(if TSH is abnormal, normal T3 and
T4 also can acceptable)
8. Female subjects of childbearing age must exclude pregnancy and are willing to use a
medically approved high-efficiency contraceptive (eg, IUD, contraceptive or condom)
during the study period and within 3 months of the last study drug administration.
9. The subject should be aware of the purpose of the study and the operations required by
the study and volunteer to participate in the study before sign the informed consent
form
Exclusion Criteria:
1. Previously exposed to other anti-angiogenic small-molecule TKI drugs, such as
pazopanib, sorafenib, regorafenib, cilnitraz, etc. or anti-angiogenic mAbs such as
bevacizumab ; or had used an anti-PD-1 antibody, an anti-CTLA-4 antibody, TCR-T, CAR-T
and other immune therapy; or 4 weeks before the first administration participated in
any other clinical trials of anticancer drugs; or before the first dose Live
attenuated vaccines are accepted within 4 weeks or during the study period.
2. Other malignant tumors have occurred in the past 3 years..
3. Immunosuppressive drugs used within 14 days prior to the first use of SHR-1210,
excluding nasal and inhaled corticosteroids or physiological doses of systemic steroid
hormones (ie, no more than 10 mg/day of turmeric or equivalent drug physiological
dose) Other corticosteroids).
4. Late-stage patients with symptomatic, disseminated to visceral, short-term risk of
life-threatening complications (including uncontrolled large amounts of exudate
[thoracic, pericardium, abdominal cavity], pulmonary lymphangitis, and more than 30%
liver involvement patients).
5. Any active autoimmune diseases or a history of autoimmune diseases (including but not
limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis,
hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, decreased
thyroid function; subjects with vitiligo or complete remission asthma in childhood and
without any intervention, all above can be included; asthma requiring medical
intervention for bronchodilators should be excluded).
6. Uncontrollable hypertension (systolic blood pressure =140 mmHg or diastolic blood
pressure =90 mmHg, despite with the optimal medical treatment.
7. Grade II or higher myocardial ischemia, myocardial infarction or poor control
arrhythmia (including male with QTc interval = 450ms, or female with QTc interval=
470ms). According to NYHA criteria, grade III to IV cardiac insufficiency, or cardiac
color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF)
<50%; myocardial infarction occurred within 6 months before enrollment, New York Heart
Association Level II or above failure, uncontrolled angina, uncontrolled severe
ventricular arrhythmia, pericardial disease with clinically significant, or
electrocardiogram suggesting acute ischemia or abnormal active conduction system.
8. Abnormal coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT >
1.5ULN), with bleeding tendency or undergoing thrombolysis or anticoagulant therapy.
9. Half of a teaspoons (2.5 ml) or more hemoptysis was found within the first 2 months or
there were significant clinical bleeding symptoms or clearly propensity bleeding
within 3 months before participant in the study, such as gastrointestinal bleeding,
hemorrhagic gastric ulcer, fecal occult blood ++ or above in baseline or vasculitis;
artery or venous thrombosis events within 6 months prior to the study, such as
cerebrovascular accidents (Including transient ischemic attacks, cerebral hemorrhage,
cerebral infarction, deep vein thrombosis and pulmonary embolism.
10. Severe infections within 4 weeks prior to accept medication (eg, intravenous infusion
of antibiotics, antifungal or antiviral drugs), or unexplained fever during
screening/first administration >38.5 °C
11. Those who have a history of psychotropic drug abuse and are unable to quit or have
mental disorders.
12. Major surgical procedures were performed within 4 weeks before the first
administration. Or open wounds or fractures.
13. There are obvious factors affecting oral drug absorption, such as inability to
swallow, chronic diarrhea and intestinal obstruction. Or sinus or perforation of empty
organs within 6 months.
14. Routine urine test indicated that urinary protein (++) or more, confirmed urinary
protein (>1.0 g) within 24 hours.
15. Patients with a history of allergy may be potentially allergic or intolerant to
Apatinib and biological agents SHR-1210.
16. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency
syndrome (AIDS), active hepatitis B (HBV DNA (> 500 IU/ml), hepatitis C (hepatitis C
antibody positive, and HCV-RNA higher than the lower limit of the analysis method) or
co-infection with hepatitis B and hepatitis C.
17. There is any situation that may damage the subject or cause the subject to fail to
meet or implement the research requirements.
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