Clinical trial NCT04303130: Camrelizumab Combined With Endostar for First-line Treatment in Subjects With Advanced Squamous NSCLC
Official title: Camrelizumab (SHR-1210) Combined With Endostar for First-line Treatment in Subjects With Advanced Squamous Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
Collaborators: name: Peking University First Hospital
name: Peking University Third Hospital
name: Beijing Shijitan Hospital, Capital Medical University
name: Chinese PLA General Hospital
name: Peking Union Medical College Hospital
name: Peking University People's Hospital
First posted: 2020-03-10
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single-arm, prospective, multi-center clinical trial. designed to evaluate patients with stage IV inability to receive or refuse chemotherapy.Efficacy and safety of first-line treatment with Camrelizumab and Endo in advanced lung squamous cell carcinoma


Eligibility criteria: Inclusion Criteria:

1. Subjects \>/= 18 years of age at the time of Informed Consent.
2. Subjects with histopathological diagnosis of squamous non-small cell lung cancer (SqNSCLC) have a histologically or cytologically confirmed stage IV (American Joint Committee on Cancer \[AJCC\] 8th edition) , and the stage IIIB/IIIC SqNSCLC that is unresectable and not fit for radical concurrent chemoradiotherapy.
3. .No prior systemic treatment. Subjects who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment free interval of at least 6 months from randomization since the last chemotherapy cycle.
4. Life expectancy of at least three months.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
6. Subjects enrolled must have measurable lesion(s) according to the RECIST 1.1 standard (the CT scan length of the tumor lesion \> 10 mm, the short diameter of CT scan of the lymph node lesions \> 15 mm).
7. The main organ function is normal. All baseline laboratory requirements will be assessed and should be obtained within -14 days of randomization. Screening laboratory values must meet the following criteria.

   1. Hemoglobin ≥ 9.0 g/dL (90 g/L)
   2. Absolute neutrophil count ≥ 2× 109/L
   3. Platelets ≥ 100× 109/L
   4. Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN)
   5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal(ULN); alkaline phosphatase ≤ 5 × ULN
   6. Serum creatinine ≤ 1× ULN or creatinine clearance \> 60 mL/minute (using Cockcroft/Gault formula)
8. Subject dosen't have unhealed wounds before enrollment.
9. Female participants of childbearing potential must have a negative serum pregnancy test within -7 days of randomization and must be willing to use very efficient barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 60 days (about 5 drug half-life + menstrual cycle) after the last dose of SHR-1210. Male participants with a female partner(s) of child-bearing potential must be willing to use very efficient barriermethods of contraception from screening through 120 days (about 5 drug half-life + sperm depletion cycle) after the last dose of SHR-1210.
10. Subjects should be voluntarily participate in clinical studies and informed consent should be signed.

Exclusion Criteria

1. Active central nervous system (CNS) metastasis and/or cancerous meningitis. Patients with treated brain metastases who were clinically stable for at least 2 weeks and have no new or advanced brain metastases may be enrolled. Patients with known untreated, asymptomatic brain metastases can be enrolled provided cerebral imaging assessment be regularly performed.
2. Subjects used immunosuppressive drugs excluding nasal spray and inhaled corticosteroids or systemic steroids at physiological doses(prednisolone≤10 mg/day or other corticosteroids of the same pharmacophysiological dose) within 14 days before the first dose.
3. Subjects with grade II or above myocardial ischemia or myocardial infarction and poorly controlled arrhythmias (QTc interval \> 450 ms for males and QTc interval \> 470 ms for females). Subjects with grade III-IV cardiac insufficiency or with left ventricular ejection fraction (LVEF) less than 50% had myocardial infarction within 6 months before admission according to NYHA criteria. Subjects with uncontrolled hypertension.
4. Participants who had any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis , Hyperthyroidism, decreased thyroid function).
5. subjects with childhood asthma has completely resolved, adults can be included without any intervention; subjects with bronchodilators for medical intervention can not be included .
6. Participants who had abnormal blood coagulation (INR\>1.5 or PT\> ULN+4s, and or APTT \> 1.5 ULN), bleeding tendency or receiving thrombolytic or anticoagulation；
7. Urine routine indicates urinary protein ≥ ++, or confirms that 24-hour urine protein is ≥1.0 g；
8. Patients with non-healing wound, non-healing ulcer, or non-healing bone fracture;
9. The patient has severe infection within 4 weeks before first administration（such as the need for intravenous antibiotics, antifungals or antivirals) and unexplained fever within 7 days before administration, ≥38.5 °C
10. There was significant coughing blood and significant clinically significant bleeding symptoms or a clear tendency to hemorrhage in the first 2 months before enrollment (such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above at baseline, or suffering from vasculitis, etc.).
11. Serious Arterial / venous thrombosis events, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, within 12 months before enrollment.
12. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection. (HBV: HBsAg positive and HBV DNA ≥ 500 IU/mL ; HVC: HCV RNA positive and abnormal liver function). And subjects with active tuberculosis.
13. History of severe hypersensitivity reactions to any component contained in Endostar or antibody preparation of Camrelizumab. And known to have severe allergic reactions to infusion reactions.
14. Any known mental illness or substance abuse that may have an impact on compliance with the test requirements;
15. There are other factors lead to patients can not participate in this clinical study by the judgment of the investigator.

Primary outcomes:
measure: PFS (Progression-Free survival)
timeFrame: 1 Year
measure: One year survival rate
timeFrame: 1 Year
Secondary outcomes:
measure: ORR (Objective control rate)
timeFrame: From the date Into this study (signed ICF) to tumor progression，assessed up to 36 months.
measure: DCR (Disease control rate)
timeFrame: From the date Into this study (signed ICF) to tumor progression，assessed up to 36 months.
measure: DOR(Duration of response）
timeFrame: From the date Into this study (signed ICF) to tumor progression，assessed up to 36 months.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jian Fang
role: PRINCIPAL_INVESTIGATOR
References: