| Eligibility |
Inclusion Criteria:
1. Aged 18-75 years, males or females;
2. Histologically or cytologically confirmed as ESCC, locally advanced and unresectable,
with local recurrence (local lymph node metastases) or distant metastases;
3. Having progressed or being intolerant to first-line systemic chemotherapy (including
chemotherapy based on cisplatin, taxol or fluorouracil). Patients are also eligible if
they progress after maintenance treatment following the first-line chemotherapy, or if
patients with postoperative recurrence or metastasis progress after concurrent
radiochemotherapy. As for the radical concurrent chemoradiotherapy,
neoadjuvant/adjuvant treatment (chemotherapy or radiochemotherapy), if patients
progress during the treatment or within six months after treatment, it is considered
as a failure of first-line treatment;
4. According to the Response Evaluation Criteria In Solid Tumour (RECIST 1.1), there is
at least one measurable lesion, which has not received any local treatment, such as
radiotherapy (if the lesion within the region of the previous radiotherapy is
confirmed to progress and satisfies RECIST1.1, it can be also selected as the target
lesion) ;
5. Tissue samples should be provided for biomarker analysis. The newly harvested tissues
are preferred. If the newly harvested tissues are not available, 5-8 archival paraffin
sections (5 um thick) can be provided;
6. ECOG: 0~1;
7. Expected survival time = 12 weeks;
8. Adequate function of major organs defined as:(1) Routine blood test: a. HB = 90 g/L;
b. ANC = 1.5 × 109/L; c. PLT = 80 × 109/L;(2) Biochemical test: a. ALB = 30 g/L; b.
ALT and AST = 2.5 ULN; if there is no liver metastasis, ALT and AST = 5 ULN; c. TBIL =
1.5ULN; d. Plasma Cr = 1.5 ULN or creatinine clearance rate (CCr) = 60 mL/min;
9. Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) = lower limit
of normal (50%).
10. Women of childbearing age should consent to take contraception measures during the
study period and within 6 months after the end of the study (eg., intrauterine device,
oral contraceptive pills or condoms). The subjects must be negative for the serum or
urine pregnancy test within 7 days before the recruitment. The female subjects must be
non-lactating women. Males should consent to take contraception measures during the
study period and within 6 months after the end of the study;
11. All subjects are recruited on a voluntary basis and sign the informed consent. They
are required to be compliant with the study and cooperative with the follow-up.
Exclusion Criteria:
1. Patients who have any active autoimmune diseases or a past history of autoimmune
diseases (including but not limited to the following: autoimmune hepatitis,
interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis,
nephritis, and hyperthyroidism; leukoderma. Subjects with fully remitted childhood
asthma and no need for any intervention during adulthood can be included; those still
having the need for bronchodilators for medical intervention cannot be included);
2. Patients who are currently on immunosuppressors or systemic hormone therapy for
immunosuppressive purposes (dose > 10 mg/day, prednisone or other hormones with
equivalent efficacy), and continue taking them within 2 weeks before recruitment;
3. ESCC patients with active bleeding in primary lesions;
4. ESCC patients in whom the primary lesions are not surgically resected and are not
shrunken in size after radiotherapy;
5. Patients who have received treatment with VEGFR inhibitors, such as sorafenib,
sunitinib, and apatinib;
6. Any of the following conditions that will interfere with oral medications: unable to
swallow, having received gastroenterectomy, chronic diarrhea and intestinal
obstruction;
7. Brain metastasis or brain metastases that have disappeared in less than 3 months;
8. Patients who have any severe and/or uncontrolled diseases, including: poor blood
pressure control (systolic pressure = 150 mmHg or diastolic pressure = 100 mmHg);
having myocardial ischemia or myocardial infarction and arrhythmia of Grade 1 and
above (including QT interval = 480 ms) and cardiac insufficiency of Grade 1; active or
uncontrollable severe infection; liver diseases, such as decompensated liver failure,
active hepatitis B (HBV-DNA = 104 copy number/mL or 2000 IU/mL) or hepatitis C
(positive for anti-HCV antibodies, and HCV-RNA higher than the lower limit of
detection with the analytical method); routine urine test indicates urine protein =++
and confirms that the 24-hour urinary protein quantification>1.0 g;
9. Patients whose wounds or bone fractures remain unhealed for a long period of time;
10. Pneumorrhagia > NCI-CTC AE Grade1 within four weeks before recruitment; bleeding at
other positions >NCI-CTC AE Grade 2 within four weeks before recruitment; having a
bleeding tendency (eg., active peptic ulcer) or currently receiving thrombolytic or
anticoagulant therapy, such as warfarin, heparin, or their analogs;
11. Patients who have experienced arterial/venous thrombotic events within six months,
such as cerebrovascular accidents (including transient ischemic attack), deep venous
thrombosis and pulmonary embolism;
12. The invasion of important blood vessels by the tumour or a high probability of the
invasion of important blood vessels by the tumor that may lead to lethal hemorrhage in
the study period ahead, as judged by the investigator according to the radiological
examination;
13. Pregnancy or lactation;
14. Patients who have a history of other malignancies in the past five years (except for
the cured basal cell carcinoma and cervical carcinoma in situ);
15. Patients who have a history of psychotropic drug abuse and unable to quit or having
mental disorders;
16. Patients who have participated in other clinical trials of drugs in the past four
weeks;
17. Patients who have concomitant diseases that may severely impair the safety of patients
or make the patients unable to complete the study, as judged by the investigator;
18. Other patients who are considered inappropriate for participation by the investigator.
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