Study of Anti-PD-1 Antibody Multimodal Combination as First-line Treatment on Time Window of Advanced Solid Tumor

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Camrelizumab/sintilimab+ Standard chemotherapy; Drug: Camrelizumab/sintilimab+ apatinib（Intolerance to chemotherapy / refuse chemotherapy）; Drug: Camrelizumab/sintilimab+ apatinib+ Standard chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jian Shi, Ph.D; Phone Number: 13831110729; Email: shijian6668@126.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Jian Shi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Drug: Camrelizumab/sintilimab+ Standard chemotherapy; Camrelizumab/sintilimab：200mg，iv，30min，d4，q3w，24 months Standard chemotherapy：Researcher chooses standard treatment by recommended guidelines，d 1-3
Experimental: Group B	Drug: Camrelizumab/sintilimab+ apatinib（Intolerance to chemotherapy / refuse chemotherapy）; Camrelizumab/sintilimab：200mg，iv，30min，d4，q3w，24 months Apatinib：250mg，d1，qd，po
Experimental: Group C	Drug: Camrelizumab/sintilimab+ apatinib+ Standard chemotherapy; Camrelizumab/sintilimab：200mg，iv，30min，d7，q3w，24 months Apatinib：250mg，d1，qd，po Standard chemotherapy：Researcher chooses standard treatment by recommended guidelines，d 1-3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Baseline to measured date of progression or death from any cause	evaluated in 24 months since the treatment began

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Baseline to measured stable disease	tumor assessment every 6 weeks since the treatment began，up to 24 months
DCR	Baseline to measured progressive disease	tumor assessment every 6 weeks since the treatment began，up to 24 months
OS	Overall survival	the first day of treatment to death or last survival confirm date,up to 24 months
Adverse events	Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. The number of Participants with adverse events will be recorded at each treatment visit.	up to 24 weeks

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital
• Investigators: Principal Investigator: Baoen Shan, Ph.D, Hebei Medical University Fourth Hospital; Principal Investigator: Jian Shi, Ph.D, Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (Actual): February 24, 2020

Study Record Updates

• Last Update Posted (Actual): December 10, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: HRHB-C001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No