Clinical trial NCT04282278: Study of Anti-PD-1 Antibody Multimodal Combination as First-line Treatment on Time Window of Advanced Solid Tumor
Official title: Study of Anti-PD-1 Antibody Multimodal Combination as First-line Treatment on Time Window of Advanced Solid Tumor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Hebei Medical University Fourth Hospital
Sponsor class: OTHER
First posted: 2020-02-24
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess time window, efficacy and safety of patients who receive anti-PD-1 antibody multimodal combination as first-line treatment of advanced solid tumor.


Eligibility criteria: Inclusion Criteria:

1. Age:18 to 70 years old;
2. Patients with advanced solid tumors confirmed by histopathology or cytology and genetic testing was negative;
3. None previous chemotherapy, Antiangiogenic targeted therapy, Immune checkpoint inhibitors therapy（NOTE: neoadjuvant and adjuvant therapy is allowed）;
4. At least one measurable lesion (measuring≥10mm on spiral CT scan, satisfying the criteria in RECIST1.1);
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
6. Life expectancy greater than or equal to 18 weeks;
7. Major organ function has to meet the following certeria:

1) For results of blood routine test HB≥90g/L; ANC≥1.5×109/L; PLT≥90×109/L; 2) For results of blood biochemical test ALB≥30g/L ALT and AST\<2.5×ULN, but\<5×ULN if the transferanse elevation is due to liver metastases； TBIL≤1.5×ULN； Serum creatinine ≤1.5×ULN; 8. Left ventricular ejection fraction (LVEF) ≥50%; 9. Women of childbearing age must have contraceptive measures or have test pregnancy (serum or urine) enroll the study before 14 days, and the results must be negative, and take the methods of contraception during the test and the last to have drugs after 8 weeks. Men must be contraception or has sterilization surgery during the test and the last to have drugs after 8 weeks; 10. Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up.

Exclusion Criteria:

1. Patients with symptomatic brain metastases;
2. Subjects with immunosuppressive medications within 14 days of first administration of study treatment, prednisone is used for less than 1 week, excluding nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (no more than 10 mg / day of prednisolone or other corticosteroids of equivalent pharmaceutical physiological dose);
3. The patient has 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; patients with vitiligo; Asthma has been completely relieved in childhood, and patients who do not need any intervention after adulthood can be included; asthma patients who require bronchodilators for medical intervention cannot be included);
4. Patients with other malignant tumors within 5 years (except for the treated skin basal cell carcinoma and cervical carcinoma in situ, dual or multiple primary tumors);
5. Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV-DNA ≥1000 IU/ml) or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the lower limit of detection of the analytical method) or co-infection with hepatitis B and C, requiring antiviral treatment during the study ;
6. 3 months before study drug administration, the following occurred: myocardial infarction, severe / unstable angina pectoris, grade III-IV cardiac insufficiency according to New York Heart Association(NYHA) criteria, uncontrolled arrhythmias (including QTcF interval male\> 450 ms, female\> 470 ms ,The QTcF interval is calculated using Fridericia formula), symptomatic congestive heart failure, cerebrovascular accidents (including transient ischemic attack or symptomatic pulmonary embolism), in stable phase, need a cardiovascular physician evaluation;
7. Severe infections within 2 weeks before study drug administration (eg. Need intravenous drip antibiotics, antifungals or antivirals) or \>38.5℃during screening visits or on the first scheduled day of dosing;
8. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
9. Less than 4 weeks from the last clinical trial;
10. History of psychiatric drugs abuse and can't quit or patients with mental disorders;
11. The researchers think inappropriate.

Primary outcomes:
measure: PFS
timeFrame: evaluated in 24 months since the treatment began
Secondary outcomes:
measure: ORR
timeFrame: tumor assessment every 6 weeks since the treatment began，up to 24 months
measure: DCR
timeFrame: tumor assessment every 6 weeks since the treatment began，up to 24 months
measure: OS
timeFrame: the first day of treatment to death or last survival confirm date,up to 24 months
measure: Adverse events
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
Study officials:
affiliation: Hebei Medical University Fourth Hospital
name: Baoen Shan, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebei Medical University Fourth Hospital
name: Jian Shi, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: