Clinical trial NCT04832204: Apatinib Combined With SHR-1210 as Second-line Treatment in Solid Tumors With Only Liver Metastases
Official title: An Exploratory Study of Apatinib Combined With SHR-1210 as Second-line Treatment in Solid Tumors With Only Liver Metastases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Solid Tumor
Keywords: After first-line treatment failed
only liver metastases
Lead sponsor: Beijing Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Chinese Society of Clinical Oncology
First posted: 2021-04-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Apatinib and SHR-1210 are new drugs produced by jiangsu hengrui pharmaceutical co., LTD. Both are listed in China. The investigators want to design a trial to explore the efficacy and safety of Apatinib and SHR-1210 in patients with solid tumors with only liver metastasis (as second-line treatment). The main purpose is to evaluate the disease progression-free survival (PFS) of Apatinib and SHR-1210 in patients with solid tumors with only liver metastasis (progress after first-line treatment). The secondary purpose is to compare the total survival period (OS); 1-year survival rate, 2-year survival rate; evaluation of drug safety; exploration of related biomarkers in specific subgroups to predict effectiveness or adverse reactions.

Detailed description: Any solid tumor in the presence of liver metastasis indicates poor prognosis, short overall survival, immunotherapy combination with anti-tumor angiogenesis agents have some curative effection according to recent studies. It seems there has been clinical evidence to improve the immune microenvironment of the tumor, while in the case of only liver metastasis, the tumor's characteristics may not be consistent with other tumors. This study was to investigate the efficacy and safety of such patients by combining Apatinib and SHR-1210. This study will include approximately 20 patients with solid tumors with only liver metastases (progression after first-line treatment). The investigators will evaluate the efficacy and safety of Apatinib combined with SHR-1210 in these patients. If possible we would check the patients' ctDNA and some infection factors.

Eligibility criteria: Inclusion Criteria:

1. age: ≥18 years old, both male and female;
2. after pathological diagnosis and first-line treatment failure of advanced solid tumor with liver metastasis only after consultation by MDT team, the patient had measurable lesions (helical CT scan ≥10mm, meeting the RECIST 1.1 standard);
3. ECOG PS: 0 \~ 1;
4. subjects' baseline blood routine and biochemical indicators shall meet the following standards: Hemoglobin ≥80g/L, Absolute neutrophils count (ANC) ≥1.5×109/L, Platelet ≥90×109/L, ALT and AST≤2.5 times normal upper limit, and liver metastasis ≤5 times normal upper limit Serum total bilirubin ≤1.5 times normal upper limit, Serum creatinine ≤1.5 times normal upper limit, Serum albumin ≥30g/L;

6) expected survival period ≥3 months; 7) women of child-bearing age must undergo a pregnancy test (serum or urine) within 7 days prior to enrollment and the result is negative, and be willing to use appropriate methods of contraception during the trial and 8 weeks after the last dose of the test drug.For men, either surgical sterilization or consent to appropriate methods of contraception during the trial and 8 weeks after the last administration of the trial drug; 8) subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

Exclusion Criteria:

1. proven allergic to apatinib and/or its excipients;
2. patients with hypertension and unable to reduce to the normal range after antihypertensive drug treatment (systolic blood pressure \>140 mmHg, diastolic blood pressure \>90 mmHg), coronary heart disease at or above grade I, grade I arrhythmia (including QTc interphase prolonging \> 450 ms in males and \> 470 ms in females) and grade I cardiac dysfunction;Patients with positive urinary protein;
3. there are multiple factors affecting oral drugs (such as inability to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.);
4. patients with a clear tendency of gastrointestinal bleeding, including the following: local active ulcer lesions, and fecal occult blood (++) is not included in the group;A history of black stool or hematemesis within 2 months;For patients with fecal occult blood (+) and no surgical resection of the primary gastric tumor, gastroscopy is required.
5. abnormal coagulation function (INR\>1.5, APTT\>1.5 ULN), with bleeding tendency;
6. patients with central nervous system metastasis;
7. pregnant or nursing women;
8. patients with other malignant tumors within 5 years;
9. patients who have a history of psychotropic substance abuse and cannot be cured or have mental disorders;
10. patients who have participated in clinical trials of other drugs within 4 weeks;
11. according to the judgment of the researcher, patients with concomitant diseases that seriously endanger the safety of patients or affect the completion of the study;
12. not suitable for inclusion.

Primary outcomes:
measure: progression-free survival
timeFrame: Patients will be followed for an average period of 1 year
Secondary outcomes:
measure: overall survival
timeFrame: Patients will be followed for an average period of 1 year
Other outcomes:
measure: 1-year survival rate
timeFrame: 12 months
measure: 2-year survival rate
timeFrame: 24 months
measure: Safety and tolerability as measured by number and grade of toxicity events
timeFrame: 12 months
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
Study officials:
affiliation: Beijing Hospital
name: Yingying Huang
role: PRINCIPAL_INVESTIGATOR
References: