Advanced Non Small Cell Lung Cancer, Soft Tissue Sarcoma, Uterine Cancer
Conditions
Keywords
immunotherapy, PD-1 checkpoint inhibitor, circulating blood tumor cells (CTC)
Brief summary
In this one-arm study, histologically or cytologically confirmed advanced NSCLC, uterine malignancies, and soft tissue sarcoma will be enrolled to investigate the efficacy and safety of PD-1 monoclonal antibody SHR-1210 and apatinib, at the same time, peripheral circulating blood tumor cells (CTC) detection and CTC-based PD-L1 antibody immunofluorescence detection will be performed.
Detailed description
Primary outcome: 1. Analysis of baseline levels of CTC and CTC PD-L1 and prognosis efficacy of patients: Objective remission rate (ORR), progression free survival (PFS), overall survival (OS); 2. Dynamic monitoring of CTC and CTC PD-L1 at baseline before treatment, after two cycles of treatment, and as the disease progresses. 3. Consistency analysis of PD-L1 and CTC PD-L1 expression in tissue specimens. Secondary outcome: Duration of response(DOR), Disease control rate(DCR), Safety of the combination therapy.
Interventions
DRUGPD-1 inhibitor
Intravenous administration of SHR1210 (200mg/2weeks or 200mg/3weeks)
DRUGApatinib
NSCLC and Uterine cancer will be given oral of Apatinib (250mg/d), soft tissue sarcoma will be given oral of Apatinib (500mg/d).
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Hunan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients fulfilling Eligibility Criteria will be included in our study. NSCLC participants will be given intravenous administration of SHR-1210 (200mg/2w) and oral of Apatinib (250mg/d) , soft tissue sarcoma will be given intravenous administration of SHR-1210 (200mg/3w) and oral of Apatinib (500mg/d), and uterine cancer will be given intravenous administration of SHR-1210 (200mg/3w) and oral of Apatinib (250mg/d). Treatments will be administrated until disease progression, death, or unacceptable toxicity.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-70 years, both men and women (Uterine cancer limited to women); 2. NSCLC: Pathologically confirmed advanced (IIIB, stage IV) NSCLC with at least 1 measurable lesion that meets the RECIST v1.1 standard without local treatment, of which stage IIIb patients are incapable, unsuitable for surgery or radical radiotherapy, NSCLC patients have failed at least the first-line standard treatment or refused to receive standard treatment, or chemotherapy intolerance, Among them, patients with sensitive gene mutations must fail after TKI treatment (patients who have failed first-line or second-line treatment may participate in this study), Patients with EGFR and ALK mutations must undergo EGFR and ALK inhibitor treatment failure and EGFR T790M mutation negative, for EGFR T790M-positive patients, third-generation EGFR TKI treatment fails. 3. Soft tissue sarcoma: Patients with distant metastasis or locally advanced disease who have previously failed chemotherapy or sensitive recurrence or metastasis to soft tissue sarcoma. Subjects who have judged by the investigator to be unsuitable for surgical treatment (including amputation) of soft tissue sarcomas (diagnosed pathologically or cytologically, but excluding gastrointestinal stromal tumors, chondrocyte-bone tumors, embryonic/acinar rhabdomyosarcoma, Juventus Sarcoma, extensive distant metastatic soft tissue tumors such as keloid cutaneous fibrosarcoma and inflammatory myofibroblastic sarcoma, malignant peripheral nerve sheath tumor, keloid cutaneous fibrosarcoma, inflammatory myofibroblastic sarcoma, malignant interstitial Dermatoma) (priority consideration: synovial sarcoma, undifferentiated multiline sarcoma, dedifferentiated liposarcoma), and measurable lesions that meet the RECIST 1.1 standard. 4. Uterine cancer: Pathologically confirmed uterine cancer, including cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma), endometrial cancer, and uterine sarcoma, at least one measurable lesion that meets RECIST 1.1 criteria, recurrence/Persons with persistent cervical cancer, endometrial cancer, and uterine sarcoma cannot be cured by surgery and/or radiotherapy, have received at least a first-line treatment for advanced (stage IVB), recurrent/persistent cervical cancer, endometrial cancer, uterine sarcoma Systemic chemotherapy patients (qualified to participate in this study after the progress of first-line chemotherapy). 5. All acute toxicity caused by previous antitumor treatments were alleviated to level 0-1 (according to NCI CTCAE version 4.03) or to the level specified by the enrollment/
Exclusion criteria
1 day before the first dose except for subjects whose toxicity does not pose a safety risk); 6. Able to provide tumor samples (at least 20 unstained tumor samples or fresh tissue specimens embedded in formalin-fixed paraffin within six months, 4ml of peripheral blood samples before treatment and each effect evaluation); 7. ECOG score: 0-1, patients with soft tissue sarcoma amputation can be relaxed to 2 points; 8. Expected survival ≥ 12 weeks; 9. The function of important organs meets the following requirements (excluding the use of any blood components and cell growth factors during screening); 1. Absolute neutrophil count ≥1.5 × 109 / L; 2. platelets ≥100 × 109/L; 3. Hemoglobin ≥9g/dL; 4. serum albumin ≥3g/dL; 5. total bilirubin ≤ 1.5ULN; 6. ALT and AST ≤1.5ULN; 7. AKP ≤ 2.5ULN; 8. Serum creatinine ≤ 1.5ULN or creatinine clearance ≥ 60mL/min; 10. Non-surgical sterilization female patients; 11. Participants volunteered to participate in the study, signed informed consent, good compliance, and cooperated with the follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | 2 years | Evaluated by researchers based on the RECIST 1.1 standard |
| The number of Circulating Tumor Cell (CTC) | 2 years | — |
| Analysis of PD-L1 expression on Circulating Tumor Cell (CTC) and tumor tissue | 2 years | — |
| Objective remission rate (ORR) | 2 years | Evaluated by researchers based on the RECIST 1.1 standard |
| Overall survival (OS) | 2 years | Evaluated by researchers based on the RECIST 1.1 standard |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate(DCR) | 2 years | Evaluated by researchers based on the RECIST 1.1 standard |
| Duration of response(DOR) | 2 years | Evaluated by researchers based on the RECIST 1.1 standard |
Countries
China
Contacts
Primary ContactNong Yang
Outcome results
None listed